Mechanisms of arm-tip regeneration in the sea star,Leptasterias hexactis

Summary Wound healing and regeneration following amputation of arm-tips of the sea star, Leptasterias hexactis, are described using light microscopy, SEM, TEM, and [³H] thymidine autoradiography. The process can be divided into a number of stages. Initially, the wound is closed by contractions of the stump-tip. Re-epithelialization then occurs through migration of epidermal cells from adjacent areas over the wound to form a thin wound epidermis. This is converted into a thicker, permanent covering in concurrence with the onset of cell cycle activity in the wound epidermis and adjacent epidermal regions. Histolysis and phagocytosis of damaged tissues occur beneath the new epidermis and a small connective tissue scar develops at the wound site within which muscle differentiates. At this time, elevated levels of [³H]thymidine incorporation are initiated in the sub-epidermal tissues of the arm-tip. A variety of differentiated cell types enter the cell cycle including cells of the parietal peritoneum, lining of the radial water canal, and the dermis. Cell division is accompanied by the development of a small new arm-tip complete with terminal ossicle, terminal tentacle, and optic cushion. The radial water canal, radial nerve, and perivisceral coelom extend by outgrowth into this newly developing tip. Accelerated growth of the regenerate then occurs in a zone just proximal to the new tip. There is no evidence of a blastema-like mass of rapidly dividing undifferentiated cells at the tip of regenerating arms. Arm-tip regeneration in this sea star may therefore be best described as a morphallactic-like process in which a true blastema is not formed, but in which scattered cell proliferation plays an essential role.     

Morphological stages of regeneration in the planarian Dugesia tigrina: A light and electron microscopic study

A precise sequence of four morphological stages of head regeneration in the planarian Dugesia tigrina has been determined by light and electron microscopy. Each stage is identified by a particular morphogenetic process: I, wound healing; II, blastema development; III, growth; IV, differentiation. A wound epidermis consisting of a thin, sheet-like layer of cells, rapidly forms from undamaged epidermal cells at the wound margin. The early blastema is comprised of neoblasts which mature into regeneration cells. The maturational changes include the appearance of a nucleolus, nuclear pores, and perinuclear dense aggregates of granulofibrillar material in these cells. These elements are not evident in the neoblasts of the younger blastema. No mitotic cells are encountered in the blastema or wound epidermis. Cytoplasmic expansion of the regeneration cells is correlated with the formation of numerous microtubules radiating from a juxtanuclear centrosphere. During differentiation of muscle cells, distended, granule-studded cisternae, having moderately fibrillar contents, are regularly disposed adjacent to small patches of myofilaments. Presumptive epidermal cells are recognized by prominent “islands” of finely fibrillar cytoplasm. These cytoplasmic zones persist for a time during definitive differentiation when Golgi bodies, vacuoles, mucous droplets, and rhabdites become evident. The newly formed epidermal cells become inserted among the cells of the wound epidermis. Thus, cells of both the blastema and of the wound epidermis contribute to the reconstituted epidermis.     

Role of epidermal stem cells in repair of partial-thickness burn injury after using Moist Exposed Burn Ointment (MEBO) histological and immunohistochemical study

Moist Exposed Burn Ointment (MEBO^®) is widely used topical agent applied on skin burn. This study investigated the effect of MEBO topical application on activation and proliferation of epidermal stem cells through the immunohistochemical localization of cytokeratin 19 (CK19) as a known marker expressed in epidermal stem cells. Biopsies from normal skin and burn wounds were taken from 21 patients with partial thickness burn 1, 4, 7, 14, 21, and 28 days after treatment with MEBO. Tissue sections were prepared for histological study and for CK19 immunohistochemical localization. In control skin, only few cells showed a positive CK19 immune-reaction. Burned skin showed necrosis of full thickness epidermis that extended to dermis. Gradual regeneration of skin accompanied with an enhancement in CK19 immune-reactivity was noted 4, 7, 14 and 21 days after treatment with MEBO. On day 28, a complete regeneration of skin was observed with a return of CK19 immune-reactivity to the basal pattern again. In conclusion, the enhancement of epidermal stem cell marker CK19 after treatment of partial thickness burn injuries with MEBO suggested the role of MEBO in promoting epidermal stem cell activation and proliferation during burn wound healing.     

Stem cells in microturbellarians

Summary A combination of microscopical, immunocytochemical, and autoradiographic techniques were employed to study stem cells and their fates during asexual reproduction and regeneration in two microturbellarians,Microstomum lineare (Macrostomida) andStenostomum leucops (Catenulida). Special attention was paid to the development of the immunoreactivity (IR) to FMRF/RF-amide and 5-HT in differentiating nerve cells.Asexual reproduction inM. lineare andS. leucops occurs by paratomy, i.e., fragmentation after completed differentiation of the new organs. Regeneration, on the other hand, involves a combination of morphallactic and epimorphic processes without the formation of a regeneration blastema. The only cells incorporating tritiated thymidine ([³H]T) were the mesenchymal and gastrodermal neoblasts, which proliferate continuously replenishing the population of stem cells available for growth, asexual reproduction and regeneration. These proliferative cells occurred in two ultrastructurally different forms, differing from each other only by the presence or absence of ciliar basal bodies in the cytoplasm. Few differentiated cells were labeled in the head piece after completed regeneration. A greater amount of labeled differentiated cells were, however, observed postpharyngeally in the first zooid as well as in zooids having developed during the same time (i.e., 20–45 h after the treatment with [³H]T). Furthermore, many labeled cells were still undifferentiated at that time or just in the beginning of the differentiation process. It can therefore be concluded that neoblasts function both as reserve cells and as functional stem cells for all differentiated cell types in these worms. IR to FMRF/RF-amide neuropeptides was not observed in nerve cells differentiating from neoblasts until the occurrence of dense-core vesicles in their cytoplasm. Due to methodological difficulties only weak or no IR to 5-HT could be traced in the nervous system of the asexual and regenerating worms.Abbreviations ICC Immunocytochemical - IR immunoreactivity - [³H]T tritiated thymidine     

Healing of skin wounds in the African catfish Clarias gariepinus

The African catfish Clarias gariepinus was used as a model for wound healing and tissue regeneration in a scale-less fish. A temporal framework of histological and cell proliferation markers was established after wound induction in the dorsolateral cranial region, by removing the epidermal and dermal layers, including stratum adiposum (SA). Wound closure and epidermis formation was initiated within 3 h post-procedure (hpp) with migration and concomitant proliferation of epidermal cells from the wound borders. The wound was covered by this primary epidermal front 12 hpp and fusion of the opposing epidermal fronts occurred within 24 hpp. Attachment of the newly formed epidermal layer to the underlying dermis was observed 48 hpp concomitant with a second wave of cell proliferation at the wound edge. Normal epidermal thickness within the wound was achieved 72 hpp. Formation of a basement membrane occurred by 120 hpp with concomitant emergence of the SA from the wound borders. Wound healing in C. gariepinus skin involved closure of the wound and re-epithelization through cell migration with a single wave of early cell proliferation not documented in other species. Furthermore, covering of the wound by epithelium as well as the reappearance of the basement membrane and SA occurred sooner than in other fish species.     

Re‐epithelialization of large wound in paedomorphic and metamorphic axolotls

Axolotls (Ambystoma mexicanum ) may heal their skin wounds scar‐free in both paedomorphs and metamorphs. In previous studies on small punch skin wounds, rapid re‐epithelialisation was noted in these two axolotl morphs. However, large wound size in mammals may affect wound healing. In this study, large circumferential full thickness excision wounds on the hind limbs were created on juvenile paedomorphic and metamorphic axolotls. The results showed re‐epithelialisation was more quickly initiated in paedomorphs than in metamorphs after wounding. The migrating rate of epidermis on the wound bed was faster in paedomorphs than in metamorphs and thus completion of re‐epithelialisation was faster in paedomorphs than in metamorphs. Within these re‐epithelialisation periods, neither basement membrane nor dermis was reformed. Epidermal cell proliferation was detected by EdU‐labelling technique. In the normal unwounded skin, epidermal proliferation rate was higher in paedomorphs than in metamorphs. After wounding, the epidermal proliferation rate was significantly lower in the migrating front on the wound bed than in the normal skin in paedomorphs. The EdU‐labelling rate between normal skin and migration front was not different in metamorphs. Lacking of more proliferating epidermal cells on the wound bed indicated that the new epidermis here derived rather from migrating epidermal cells than from cell proliferation in situ. In conclusion, re‐epithelialisation in the large wound might be fully completed in both morphs despite it was initiated earlier and with faster rate in paedomorphs than in metamorphs. The new epidermis on the wound bed derived mainly from cell migration than by cell proliferation in the re‐epithelialisation period. J. Morphol. 278:228–235, 2017. © 2016 Wiley Periodicals,Inc.     

Ultraviolet B irradiation induces epidermal regeneration with rapidly cycling cells

Abstract. The left flank of hairless mouse skin was irradiated with a minimal erythema dose of ultraviolet B (UVB) light at 297 nm (25 mJcm^-2), while the right flank served as untreated control. The alterations in epidermal growth kinetics induced by this UVB dose were studied with the percentage of labelled mitoses (PLM) technique during the period of increased proliferation. Thirty hours after irradiation, when a large cohort of cells appears in S phase, each animal was injected intra-peritoneally with 50 /iCi tritiated thymidine ([³H]-TdR). The number of labelled basal and suprabasal cells, as well as their localization in epidermis were registered in histological sections at short intervals up to 48 h after the [³H]-TdR pulse. Labelled mitoses were also counted in the same specimens. The results showed a four-fold increase of the high initial number of labelled cells in UVB-exposed epidermis within 18 h of the pulse injection, and a sixfold increase after 36 h. In control epidermis, where the starting value of the labelling index was much lower, there was only a three to four-fold increase in the number of labelled cells during the period studied. The PLM and the labelling index data were consistent with an average cell cycle time of approximately 10–12 h for UVB-exposed cells, in contrast to about 30 h for the fastest cycling population in control epidermis. The PLM curve also indicated a prolonged S phase duration in UVB-exposed epidermis compared with controls. In addition, labelled cells were seen in the suprabasal layer as early as 6 h after the [³H]-TdR injection and within 36 h labelled cells had reached the outermost layer of nucleated cells, indicating a reduced transit time through epidermis. The present study shows that a minimal erythema dose of UVB light at 297 nm induced a period of increased transit time through the S phase, combined with rapid cell proliferation, leading to an overall shortening of the epidermal cell cycle time. The cohort of cells labelled with [³H]-TdR 30 h after irradiation seemed to proceed as a wave of partially synchronized cells through the cell cycle for more than two rounds, which is comparable with the cell kinetic perturbations observed in regenerating mouse epidermis.     

Vitamin D and calcium signaling in epidermal stem cells and their regeneration

Epidermal stem cells (SCs) residing in the skin play an essential role for epidermal regeneration during cutaneous wound healing. Upon injury, distinct epidermal SCs residing in the interfollicular epidermis and/or hair follicles are activated to proliferate. Subsequently, SCs and progeny migrate, differentiate and restore the epidermis. We review a role of the vitamin D signaling through its receptor of vitamin D receptor (Vdr) in these processes. Vdr conditional knockout (cKO) mouse skin experiences a delay in wound re-epithelialization under low dietary calcium conditions, stimulating our efforts to examine a cooperative role of Vdr with calcium signaling through the calcium sensing receptor in the epidermis. We review the role of vitamin D and calcium signaling in different processes essential for injury induced epidermal regeneration during cutaneous wound repair. First, we discuss their roles in self-renewal of epidermal SCs through β-catenin signaling. Then, we describe epidermal remodeling, in which SCs and progeny migrate and differentiate to restore the epidermis, events controlled by the E-cadherin mediated adherens junction signaling. Finally, we discuss the potential mechanisms for vitamin D and calcium signaling to regulate injury induced epidermal regeneration mutually and interdependently.     

Characterization of a newin vitro model for studies of reepithelialization in human partial thickness wounds

Summary Reepithelialization of artificial partial thickness wounds made in biopsies of human skin was determined after 3, 5, or 7 d of incubation, submerged or elevated to the air-liquid interface. The biopsies were reepithelialized within 5–7 d, with a more complete epidermal healing in wounds exposed to air. Both types of wounds showed similar time-course in deposition of basement membrane components, as detected by immunofluorescence labeling. Laminin and collagen type VII were deposited underneath the migrating tips, whereas collagen type IV was detected after reepithelialization. Markers of terminal differentiation showed a pattern close to normal in the air-liquid incubated wounds after reepithelialization. Involucrin was detected in the suprabasal regions of the migrating epidermis and thereafter in the upper half of neo-epidermis in the air-liquid incubated wound. Filaggrin could not be detected in the submerged wounds at any time during healing, whereas wounds exposed to air showed a well-differentiated epidermis by Day 7. Tritiated thymidine-incorporation indicated proliferation of epidermal and dermal cells during reepithelialization and a maintained viability, as shown by cultivation of endothelial- and fibroblast-like cells obtained from the dermis 7 d after wounding. Reepithelialization in this humanin vitro model is supported by a matrix close to normal with the possibility of extracellular influences and cell-cell interactions and, in addition, the technique is simple and reproducible. Therefore, we suggest this model for studies of regeneration in culture and as a complement toin vivo studies on epidermal healing.     

Asexual reproduction in Microstomum lineare (Turbellaria). I. An autoradiographic and ultrastructural study

The distribution of cells preparing for proliferation during asexual reproduction by paratomy in Microstomum lineare (Turbellaria) was investigated using the technique of exogenous tritiated thymidine ([³H]T) labelling and routine electron microscopy. The subsequent fates of labelled cells in developing and mature zooids were followed by fixing tissues at various intervals. The only labelled cells are mesenchymal and gastrodermal neoblasts, occurring along the whole worm without any special growth zones or axial gradient. Organ primordia develop as a result of locally dividing as well as of migrating cells.     

玉米叶表皮短细胞发育过程的形态特征及栓质细胞作用研究

采用大田试验,直接撕表皮或对叶片进行固定处理,结合单染、复染、荧光染色等多种细胞学显色方法,利用光学显微镜、荧光显微镜和扫描电子显微镜系统观察玉米叶表皮短细胞的发生时期、发育过程、分布规律以及形态结构特征,研究K⁺和H₂O₂在栓质细胞中的分布变化与表皮其它细胞中K⁺和H₂O₂的分布及气孔器开关的关系,为进一步挖掘短细胞的新功能提供细胞学依据。结果表明：（1）短细胞是同步发生在玉米多叶位新表皮组织形成过程中,所有植株从第7新生叶,大部分第6叶,极少数第5叶的基部同时开始发生短细胞,之后新生的高位叶也均发生短细胞,并随着叶位的升高叶片各部位短细胞密度均增大,所有植株的1~4叶（因不再生长）均无短细胞出现。（2）初期发育的叶表皮细胞进行不对称分裂,生成相互交替的长、短细胞,有的短表皮细胞横（垂直叶脉）分裂,形成栓质细胞和硅质细胞对;栓质细胞基部与叶肉细胞相邻,硅质细胞嵌在栓质细胞和表皮细胞间偏上。（3）有短细胞发生的叶片,宏观背面发亮且覆有蜡质层,微观表皮细胞的着色特性发生了变化;栓质细胞为面包形柱状细胞,硅质细胞为哑铃形扁细胞。（4）气孔器张开时,栓质细胞中没有K⁺和H₂O₂的积累;气孔器关闭时,栓质细胞中积累了大量的K⁺和H₂O₂,且栓质细胞中K⁺和H₂O₂的积累始终与副卫细胞中K⁺和H₂O₂的积累变化一致,而硅质细胞和长细胞没有K⁺和H₂O₂的积累。该研究确定了玉米叶表皮短细胞发生的时期;展示了其发育过程的形态学变化特征;发现栓质细胞中K⁺和H₂O₂的积累随气孔器开关呈周期性变化,且与副卫细胞中K⁺和H₂O₂的积累变化保持一致。     

A transgenic reporter under control of an es1 promoter/enhancer marks wound epidermis and apical epithelial cap during tail regeneration in Xenopus laevis tadpole

Rapid wound healing and subsequent formation of the apical epithelial cap (AEC) are believed to be required for successful appendage regeneration in amphibians. Despite the significant role of AEC in limb regeneration, its role in tail regeneration and the mechanisms that regulate the wound healing and AEC formation are not well understood. We previously identified Xenopus laevis es1, which is preferentially expressed in wounded regions, including the AEC after tail regeneration. In this study we established and characterized transgenic Xenopus laevis lines harboring the enhanced green fluorescent protein (EGFP) gene under control of an es1 gene regulatory sequence (es1:egfp).The EGFP reporter expression was clearly seen in several regions of the embryo and then declined to an undetectable level in larvae, recapitulating the endogenous es1 expression. After amputation of the tadpole tail, EGFP expression was re-activated at the edge of the stump epidermis and then increased in the wound epidermis (WE) covering the amputation surface. As the stump started to regenerate, the EGFP expression became restricted to the most distal epidermal region, including the AEC. EGFP was preferentially expressed in the basal or deep cells but not in the superficial cells of the WE and AEC.We performed a small-scale pharmacological screening for chemicals that affected the expression of EGFP in the stump epidermis after tail amputation. The EGFP expression was attenuated by treatment with an inhibitor for ERK, TGF-β or reactive oxygen species (ROS) signaling. These treatments also impaired wound closure of the amputation surface, suggesting that the three signaling activities are required for es1 expression in the WE and successful wound healing after tail amputation.These findings showed that es1:egfp Xenopus laevis should be a useful tool to analyze molecular mechanisms regulating wound healing and appendage regeneration.     

Epithelial stem cells and implications for wound repair

Activation of epithelial stem cells and efficient recruitment of their proliferating progeny plays a critical role in cutaneous wound healing. The reepithelialized wound epidermis has a mosaic composition consisting of progeny that can be traced back both to epidermal and several types of hair follicle stem cells. The contribution of hair follicle stem cells to wound epidermis is particularly intriguing as it involves lineage identity change from follicular to epidermal. Studies from our laboratory show that hair follicle-fated bulge stem cells commit only transient amplifying epidermal progeny that participate in the initial wound re-epithelialization, but eventually are outcompeted by other epidermal clones and largely disappear after a few months. Conversely, recently described stem cell populations residing in the isthmus portion of hair follicle contribute long-lasting progeny toward wound epidermis and, arguably, give rise to new interfollicular epidermal stem cells. The role of epithelial stem cells during wound healing is not limited to regenerating stratified epidermis. By studying regenerative response in large cutaneous wounds, our laboratory uncovered that epithelial cells in the center of the wound can acquire greater morphogenetic plasticity and, together with the underlying wound dermis, can engage in an embryonic-like process of hair follicle neogenesis. Future studies should uncover the cellular and signaling basis of this remarkable adult wound regeneration phenomenon.     

Growth potential of Rana tigerina skin lipids in cell cultures

Summary This study involves the investigation of the lipid composition of the skin of Rana tigerina which has a significant healing capacity. The results indicated that the lipid extract enhanced keratinocyte and fibroblast cell proliferation progressively and were found to be much more efficient in comparison to agents known to cause cell proliferation and to be anti-inflammatory such as hydrocortisone. Cell proliferation was dose dependent and suppression occurred only at very high doses. [³H]thymidine incorporation studies produced the same results. Because proliferation, migration, and differentiation of the basal cells is essential for initiation and progression of wound healing, any agent enhancing their proliferation would hasten the healing process. This paper therefore aims at elucidating the effect of composition of the total lipid extract confirming the efficacy of frog skin in wound healing and thereby providing an understanding of the natural mechanism of healing.     

Scanning electron microscopical observations on epidermal wound healing in the PlanarianDugesia tigrina

Summary Epidermal wound healing in regeneratingDugesia tigrina (Planaria) has been studied using scanning electron microscopy (SEM). The normal epidermal surface and its differentiations have been descrebed. Observations on living material reveal the highly dynamic state of the wound in invididual animals and its more or less continously changing size due to the state of activity of the animals. These observations show good agreement with the SEM studies, which allow a clear delineation of cellular details of the wound, the wound margins and the apposing epidermal regions. These details are described. The over-all picture of planarian wound healing that emerges is briefly as follows: Epithelization is characterized by absence of proliferation from the old intact epidermis. Variable contraction of smooth muscle cells reduces the wound size to a certain extent. Simultaneously with this and also during a longer period epidermal cells adjacent to the wound are extending and some become highly attenuated. These two processes together are only to a certain degree effective in wound closure because of a definite epidermal cell deficit which is reflected in the emergence of an epidermal wound edge reflecting the maximal contribution of these two processes to an attempt to close the wound. Complete epithelization is effected by the operation of a third mechanism: Recruitment of cell through flow of subjacent blastemal cells (including rhabdite-forming cells) along the wound border; these cells subsequently occupy a peripheral position in the wound. This process is supplemented by cell immigration and insertion into the adjacent old epidermis and in the wound cell sheet. Rhabdite-forming cells contribute predominantly to this process. Eventually integration between old epidermal cells and the newly recruited cells which differentiate into epidermal cells results in final epithelization. Complete wound healing is based on interactions between the epidermal cell system and the regenerating subepidermal membrane-connective tissue filament-muscle cell system.     

The relationship between cell division and melanocyte differentiation in epidermal cultures from mouse embryos

Cultures of 14-day embryonic mouse epidermis that include melanoblasts initiate melanin synthesis 30 hr after plating, a schedule that is 2.5 days earlier than in vivo. In order to determine if the accelerated differentiation of melanoblasts is related to a cessation of cell proliferation in the cultures, a study of [³H]thymidine incorporation by melanoblasts and melanocytes was made. Autoradiograms of 14-day epidermal cultures grown for 48 hr in medium containing [³H]thymidine revealed that melanoblasts continue to proliferate during this time period. A second population of melanoblasts that did not incorporate [³H]thymidine was also present in these cultures. The relative numbers of dividing and nondividing melanoblasts change with the age of the epidermis cultured. Ninety-one percent of the melanoblasts in 13-day epidermis take up [³H]thymidine, 63% incorporate [³H]thymidine in 14-day cultures, and only 29% take up label in cultures of 15-day epidermis. It appears from these results that melanoblasts during their migration from the neural crest are proliferative cells and that during the early invasion of the epidermis a nonproliferative population of melanoblasts is established. Both populations coexist in the epidermis and subsequently undergo differentiation on the same time schedule.     

Effects of degranulation of mast cells on proliferation of mesenchymal cells in the mesentery of mice

Summary A mast-cell activator, compound 48/80, causes proliferation of mesenchymal cells in the mesentery of rats. Its effect on W/W ^vmice deficient in mast cells was tested to determine whether the proliferation is mediated in the degranulation of mast cells. Incorporation of [³H]thymidine into mesenchymal cells in the mesentery of these mice with or without compound 48/80 was very small compared to their normal litter mates. However, bone marrow transplantation markedly enhanced the effect of compound 48/80, and resulted in an incorporation of [³H]thymidine almost comparable to that observed in normal mice. Our results provide evidence that mesenchymal cell proliferation is caused by a product secreted by mast cells when stimulated by compound 48/80.Supported by a Grant-in-Aid for Scientific Research, No. 366, from the Japanese Ministry of Health and WelfareThe authors are indebted to Drs. Motomu Minamiyama and Yukio Hirata for valuable advices, and to Miss Mitsuko Inoue for technical assistance     

The plasminogen receptor,Plg-RKT,plays a role in inflammation and fibrinolysis during cutaneous wound healing in mice

Wound healing is a complex physiologic process that proceeds in overlapping, sequential steps. Plasminogen promotes fibrinolysis and potentiates the inflammatory response during wound healing. We have tested the hypothesis that the novel plasminogen receptor, Plg-R_KT, regulates key steps in wound healing. Standardized burn wounds were induced in mice and time dependence of wound closure was quantified. Healing in Plg-R_KT^−/− mice was significantly delayed during the proliferation phase. Expression of inflammatory cytokines was dysregulated in Plg-R_KT^−/− wound tissue. Consistent with dysregulated cytokine expression, a significant delay in wound healing during the proliferation phase was observed in mice in which Plg-R_KT was specifically deleted in myeloid cells. Following wound closure, the epidermal thickness was less in Plg-R_KT^−/− wound tissue. Paradoxically, deletion of Plg-R_KT, specifically in keratinocytes, significantly accelerated the rate of healing during the proliferation phase. Mechanistically, only two genes were upregulated in Plg-R_KT^−/− compared with Plg-R_KT^+/+ wound tissue, filaggrin, and caspase 14. Both filaggrin and caspase 14 promote epidermal differentiation and decrease proliferation, consistent with more rapid wound closure and decreased epidermal thickness during the remodeling phase. Fibrin clearance was significantly impaired in Plg-R_KT^−/− wound tissue. Genetic reduction of fibrinogen levels to 50% completely abrogated the effect of Plg-R_KT deletion on the healing of burn wounds. Remarkably, the effects of Plg-R_KT deletion on cytokine expression were modulated by reducing fibrinogen levels. In summary, Plg-R_KT is a new regulator participating in different phases of cutaneous burn wound healing, which coordinately plays a role in the interrelated responses of inflammation, keratinocyte migration, and fibrinolysis.Subject terms: Extracellular matrix, Mechanisms of disease     

Differences between normal and scaleless (sc/sc) chicken epidermal cell surfaces detected with wheat germ agglutinin

Dissociated epidermal cells derived from the backskin of scaleless chick embryos (stage 34 or 35) form larger agglutinates with wheat germ agglutinin (WGA) than epidermal cells from normal embryonic skin. [³H]Acetyl WGA binding to the scaleless cells is twice as great as to normal epidermal cells. Treatment of these cells with concanavalin A (conA) results in equivalent agglutination of both mutant and normal epidermal cells, whereas neither scaleless nor normal epidermal cells are agglutinated by Dolichos biflorus agglutinin (DBA), soybean agglutinin (SBA) or Ulex europeus agglutinin (UEA). This alteration in cell surface carbohydrates may be related to the failure of the scaleless mutant embryonic epidermis to undergo normal morphogenesis.