角质细胞生长因子研究进展

角质细胞生长因子(KGF)从属于成纤维细胞生长因子家族。KGF基因表达受多种细胞因子调控。KGF与受体KGFR特异性的结合发挥其多种生物学功能：参与组织、器官的发育;参与皮肤、胃、肠、肾、膀胱、肺等上皮的损伤修复;减少放、化疗所带来的副作用,具有损伤防护功能;KGF与肿瘤密不可分。     

角质细胞生长因子的研究进展

角质细胞生长因子（KGF）是成纤维细胞生长因子（FGFs）家族的成员,即FGF－7,最初是从人胚胎肺成纤维细胞的培养上清中分离纯化获得的。成熟KGF为一163个氨基酸残基的单链多肽,分子量为26－28KD。KGF由各种来源的间质细胞分泌,受体分布于上皮细胞,其生物学活性是特异性地促进上皮细胞的增殖、迁移和分化。FGF的表达受激素和一些细胞因子的调控。有关研究表明,KGF对肺泡Ⅱ型细胞的增殖以及皮肤、胃肠道粘膜和角膜损伤的修复具有十分重要的作用。     

角质细胞生长因子-2研究进展

角质细胞生长因子 2 (KGF 2 )也叫成纤维细胞生长因子 10 (FGF 10 ) ,是成纤维细胞生长因子家族的一员 .能特异性促进上皮细胞的增殖、分化和迁移 ,对脊椎动物多种组织和器官的发育起重要调控作用 ,对临床上多种疾病的治疗也有很好的应用前景 .1　KGF 2与受体KGF 2有两种细胞膜表面受体 :FGFR1Ⅲb和FGFR2Ⅲb .KGF 2与FGFR2Ⅲb的亲和力很高 ,而与FGFR1Ⅲb的亲和力很低 ,只有在高浓度KGF 2存在时才与FGFR1Ⅲb结合 .KGF 2与受体结合后 ,促使受体胞内的C端酪氨酸残基磷酸化 ,磷酸化的受体具有了酪氨酸蛋白激酶活性 ,并与一系…     

角质细胞生长因子及其对消化道损伤的防治作用

角质细胞生长因子（KGF）是成纤维细胞生长因子家族的一员,它通过与KGF受体（KGFR）的结合,特异性地刺激上皮细胞的增殖,对皮肤、胃、肠、肾、膀胱、肺等上皮的损伤有修复作用,能减少放、化疗所带来的副作用。目前研究较多的是KGF对消化道损伤的防护以及损伤后的治疗作用。     

角质细胞生长因子的研究进展

角质细胞生长因子(KGF)是成纤维细胞生长因子(FGFs)家族的成员,即FGF-7,最初是从人胚胎肺成纤维细胞的培养上清中分离纯化获得的。成熟KGF为一163个氨基酸残基的单链多肽,分子量为26—28KD。KGF由各种来源的间质细胞分泌,受体分布于上皮细胞,其生物学活性是特异性地促进上皮细胞的增殖、迁移和分化。KGF的表达受激素和一些细胞因子的调控。有关研究表明,KGF对肺泡Ⅱ型细胞的增殖以及皮肤、胃肠道粘膜和角膜损伤的修复具有十分重要的作用。     

角质细胞生长因子(KGF)研究进展

角质细胞生长因子(KGF)属于成纤维细胞生长因子(FGFs)家族的成员之一,又称FGF一7,最早由Rubin等(1980)从人类胎肺成纤维细胞培养液中分离提纯获得的。人KGF的cDNA编码一含194个氨基酸的单链多肽,其分子量为26-28KD。KGF由各种来源的间质细胞分泌,与肝素有较强的亲和力,其受体KGFR属于蛋白酪氨酸激酶受体家族,目前已知该家族主要包括FGFR1、FGFR2、FGFR3和FGFR4四位成员,KGFR由FGFR2基因编码,为FGFR-2的剪接形式,即FGFR2Ⅲb,其主要分布于上皮细胞,KGF与靶细胞膜上的受体KGFR特异性结合后,促使受体自身磷酸化,从而启动细胞内信号级联反应,进而发挥多种生物学功能:参与组织器官发育、促进细胞增殖及组织损伤修复、减少放化疗引起的副反应,尤其与癌症的发生发展有着密切的联系。该文就KGF的研究进展进行综述。     

肺部铜绿假单胞菌感染前后肺组织角质细胞生长因子的变化研究

目的观察与分析肺部铜绿假单胞菌（PAE）感染前后患者肺组织角质细胞生长因子（KGF）的变化情况,并研究其临床意义。方法将2010年12月到2013年12月于沈阳军区总医院接受治疗的60例肺炎患者作为研究对象,分别于其感染前后收集肺组织标本,检测感染前后患者肺组织角质细胞生长因子的表达水平。结果在感染PAE后,患者肺组织角质细胞生长因子蛋白表达水平呈明显上升的态势,并于感染3 d后到达峰值。相较感染铜绿假单胞菌前,患者肺组织角质细胞生长因子蛋白表达水平明显提升,感染前后对比差异有统计学意义（P〈0.05）。结论在急性肺损伤的诊断与治疗中,重视对患者肺组织KGF蛋白表达水平的研究,及时实施KGF辅助干预,对抑制感染,控制肺炎的进展有十分重要的作用。     

角质形成细胞生长因子-2的应用研究进展

角质形成细胞生长因子-2（KGF-2）是成纤维细胞生长因子（FGFs）超家族中角质细胞生长因子家族的一员。KGF-2能够促进上皮细胞的增殖、分化和迁移,参与并调控脊椎动物多种组织和器官的形成。本文就其生物学功能,以及在疾病治疗和临床试验等方面的研究进展进行综述。     

金雕肺的组织结构及KGF、c-Fos和Bax的表达

为了解金雕(Aguila chrysaetos)肺的组织结构特征,观察角质细胞生长因子(KGF)、c-Fos蛋白和Bax蛋白在肺中的表达情况,应用生物显微技术和免疫组织化学方法观察了金雕肺的组织结构,检测KGF、c-Fos和Bax蛋白在肺中的表达.结果表明,金雕的肺由各级支气管及其周围的呼吸毛细管组成,肺房呈辐射状开口于三级支气管周围,呼吸毛细管相互吻合成网状,周围有丰富的毛细血管网.KGF、c-Fos和Bax在三级支气管、肺房和呼吸毛细管的上皮细胞中呈免疫反应阳性,三者的表达强度有差异.KGF、c-Fos和Bax可能发挥不同的功能,它们的协同表达可能调控鸟肺细胞的生长、发育及成熟.     

重组人角质细胞生长因子-2基因克隆、表达、纯化与活性分析

 从人胚肺二倍体细胞KMB17中抽提总RNA ,经RT PCR扩增获得编码人角质细胞生长因子 2 (keratinocytegrowthfactor 2 ,KGF 2 )的cDNA .克隆于硫氧环蛋白表达载体pThioHisA ,序列分析表明与文献报道一致 .经IPTG诱导 ,在大肠杆菌BL2 1中实现高效表达 ,表达量可达菌体总蛋白 10 %～15 % .菌体超声破碎 ,上清经CM SepharoseFF阳离子交换 ,Heparin Sepharose亲和层析 ,Superdex 75凝胶过滤层析纯化得到重组人KGF 2 ,纯度高于 95 % .生物活性分析表明 ,它能够促进成纤维细胞NIH 3T3的增殖 ,诱导鸡胚背根神经结神经轴突的生长 ,促进鸡胚尿囊膜血管生成 .研究结果表明 ,获得了 95 %纯度的具有生物学活性的重组人KGF 2 ,为进一步的基础与应用研究提供了基础     

Paracrine effects of bFGF and KGF on the process of mouse blastocyst implantation

Implantation is a complex process that requires the interaction of the blastocyst, and subsequently, that of the developing embryos with the endometrium. Several growth factors and cytokines are involved in implantation, but the details of their actions as related to the regulation of blastocyst implantation remain unclear. In the present study, the RT-PCR method was used to determine the gene expression of basic fibroblast growth factor (bFGF), keratinocyte growth factor (KGF), FGF receptor 1 (FGFR1), FGF receptor 2 (FGFR2), and KGF receptor (KGFR) in mouse embryos and in the stromal and epithelial cells of the uterine endometrium. Basic FGF and KGF mRNA were expressed in the endometrial cells, but were not expressed in the embryos. The mRNAs of receptors for bFGF and KGF were expressed in the blastocysts and in the in vitro implanting embryos, suggesting that bFGF and KGF may exert paracrine effects on blastocyst implantation. In this mouse model of blastocyst implantation, it was found that transforming growth factor α (TGF-α) at the concentrations of 1 ng/ml and 10 ng/ml significantly enhanced the blastocyst attachment and trophoblast spreading and increased trophoblast surface area. Relatively high concentrations of bFGF (100–500 ng/ml) significantly enhanced the rates of blastocyst attachment and of trophoblast spreading and promoted the expansion of the surface area of the implanting embryos. Unlike the rates of blastocyst attachment and trophoblast spreading, the surface area of the spreading embryos was significantly increased by addition of KGF (1–100 ng/ml). These results suggest that the bFGF and KGF derived from the endometrial cells exert paracrine effects on the process of implantation by stimulating trophoblast outgrowth through their cognate receptors. Mol. Reprod. Dev. 50:54–62, 1998. © 1998 Wiley-Liss, Inc.     

Keratinocyte growth factor promotes preadipocyte proliferation via an autocrine mechanism

Keratinocyte growth factor (KGF; also known as FGF‐7) is a well‐characterized paracrine growth factor for tissue growth and regeneration. However, its role in adipose tissue, which is known to undergo tremendous expansion in obesity, is virtually unknown. Given that we previously identified KGF as one of the up‐regulated growth factors in adipose tissue of an early‐life programmed rat model of visceral obesity, the present study was undertaken to examine the hypothesis that KGF promotes adipogenesis. Using 3T3‐L1 and rat primary preadipocytes as in vitro model systems, we demonstrated that (1) KGF stimulated preadipocyte proliferation in a concentration‐dependent manner with a maximal effect at 2.5 ng/ml (～2‐fold increase); (2) KGF mRNA was highly expressed in rat adipocytes and preadipocytes as well as 3T3‐L1 cells; (3) treatment of preadipocytes with a neutralizing antibody against KGF and siRNA‐mediated knockdown of KGF led to a 50% reduction in their proliferative capacity; (4) KGF activated the protein kinase Akt, and the PI3 kinase inhibitor LY294002 blocked KGF stimulation of preadipocyte proliferation; and (5) KGF did not promote differentiation of preadipocytes to mature adipocytes. Together, these results reveal adipocytes and their precursor cells as novel sites of KGF production. Importantly, they also demonstrate that KGF promotes preadipocyte proliferation by an autocrine mechanism that involves activation of the PI3K/Akt signaling pathway. Aberrant KGF expression may have consequences not only for normal adipose tissue growth but also for the pathogenesis of obesity. J. Cell. Biochem. 109: 737–746, 2010. © 2010 Wiley‐Liss, Inc.     

Keratinocyte growth factor receptor ligands target the receptor to different intracellular pathways

The keratinocyte growth factor receptor (KGFR)/fibroblast growth factor receptor 2b is activated by high-affinity-specific interaction with two different ligands, keratinocyte growth factor (KGF)/fibroblast growth factor (FGF)7 and FGF10/KGF2, which are characterized by an opposite requirement of heparan sulfate proteoglycans and heparin for binding to the receptor. We investigated here the possible different endocytic trafficking of KGFR, induced by the two ligands. Immunofluorescence and immunoelectron microscopy analysis showed that KGFR internalization triggered by either KGF or FGF10 occurs through clathrin-coated pits. Immunofluorescence confocal microscopy using endocytic markers as well as tumor susceptibility gene 101 (TSG101) silencing demonstrated that KGF drives KGFR to the degradative pathway, while FGF10 targets the receptor to the recycling endosomes. Biochemical analysis showed that KGFR is ubiquitinated and degraded after KGF treatment but not after FGF10 treatment, and that the alternative fate of KGFR might depend on the different ability of the receptor to phosphorylate the fibroblast growth factor receptor substrate 2 (FRS2) substrate and to recruit the ubiquitin ligase c-Cbl. The recycling endocytic pathway followed by KGFR upon FGF10 stimulation correlates with the higher mitogenic activity exerted by this ligand on epithelial cells compared with KGF, suggesting that the two ligands may play different functional roles through the regulation of the receptor endocytic transport.     

Scarless wound healing: Current insights from the perspectives of TGF-β, KGF-1, and KGF-2

The process of wound healing involves a complex and vast interplay of growth factors and cytokines that coordinate the recruitment and interaction of various cell types. A series of events involving inflammation, proliferation, and remodeling eventually leads to the restoration of the damaged tissue. Abrogation in the regulation of these events has been shown to result in excessive scarring or non-healing wounds. While the process of wound healing is not fully elucidated, it has been documented that the early events of wound healing play a key role in the outcome of the wound. Furthermore, high levels of inflammation have been shown to lead to scarring. The regulation of these events may result in scarless wound healing, especially in adults. The inhibition of transforming growth factor-β (TGF-β) and the administration of keratinocyte growth factors (KGF), KGF-1 and KGF-2, has in recent years yielded positive results in the acceleration of wound closure and reduced scarring. Here, we encapsulate recent knowledge on the roles of TGF-β, KGF1, and KGF2 in wound healing and scar formation and highlight the areas that need further investigation. We also discuss potential future directions for the use of growth factors in wound management.     

角质形成细胞生长因子(KGF)在喉粘膜良性、癌前及恶性病变中的mRNA水平分析

利用原位杂交的方法检测KGFmRNA在正常喉粘膜上皮（N）、慢性非特异性炎症（IF）、不典型增生（DYS）及鳞癌（SCC）中的转录水平,探讨KGF在喉粘膜良性及恶性病变中的分布和可能的作用。结果表明,KGFmRNA不仅在间质中的成纤维细胞中表达,少量的炎细胞及血管内皮细胞中亦表达,而且从N、IF、DYS到SCC、KGFmRNA转录水平逐渐增强;上皮细胞及肿瘤性上皮细胞不表达KGFmRNA,KGFmRNA在分化差的SCC周围间质中表达较分化好的SCC周围间质增多。结论：KGF在上皮与间充质细胞的交互作用中发挥着重要的作用,对维持喉粘膜正常结构、代谢及喉癌的发生发展具有重要意义。     

Cortactin involvement in the keratinocyte growth factor and fibroblast growth factor 10 promotion of migration and cortical actin assembly in human keratinocytes

Keratinocyte growth factor (KGF/FGF7) and fibroblast growth factor 10 (FGF10/KGF2) regulate keratinocyte proliferation and differentiation by binding to the tyrosine kinase KGF receptor (KGFR). KGF induces keratinocyte motility and cytoskeletal rearrangement, whereas a direct role of FGF10 on keratinocyte migration is not clearly established. Here we analyzed the motogenic activity of FGF10 and KGF on human keratinocytes. Migration assays and immunofluorescence of actin cytoskeleton revealed that FGF10 is less efficient than KGF in promoting migration and exerts a delayed effect in inducing lamellipodia and ruffles formation. Both growth factors promoted phosphorylation and subsequent membrane translocation of cortactin, an F-actin binding protein involved in cell migration; however, FGF10-induced cortactin phosphorylation was reduced, more transient and delayed with respect to that promoted by KGF. Cortactin phosphorylation induced by both growth factors was Src-dependent, while its membrane translocation and cell migration were blocked by either Src and PI3K inhibitors, suggesting that both pathways are involved in KGF- and FGF10-dependent motility. Furthermore, siRNA-mediated downregulation of cortactin inhibited KGF- and FGF10-induced migration. These results indicate that cortactin is involved in keratinocyte migration promoted by both KGF and FGF10.