The signaling pathway of stromal cell-derived factor-1 and its role in kidney diseases

Abstract

The chemokine stromal cell-derived factor-1 (SDF-1) regulates the trafficking of progenitor cell (PGC) during embryonic development, cell chemotaxis, and postnatal homing into injury sites. SDF-1 also regulates cell growth, survival, adhesion and angiogenesis. However, in different tissues/cells, the role of SDF-1 is different, such as that it is increased in most of the tumors and associated with cancer metastasis, whereas it is essential for the development of vasculature. For kidney diseases, its role remains controversial. Signaling pathways might be very important in the pathogenesis of kidney diseases. We performed this review to provide a relatively complete signaling pathway flowchart for SDF-1 to the investigators who were interested in the role of SDF-1 in the pathogenesis of kidney diseases. Here, we reviewed the signal transduction pathway of SDF-1 and its role in the pathogenesis of kidney diseases.     

The signaling pathway of NADPH oxidase and its role in glomerular diseases

Abstract

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), a major source of reactive oxygen species, is a critical mediator of redox signaling. It is well-documented that oxidative stress is associated with the development of glomerular diseases (GN). Hence, the Nox was also thought to be involved in the pathogenesis of GN. However, the expression of Nox in various GN was not consistent, the mechanisms by which the activity of the Nox enzymes in regulating renal cells remains unclear. Signaling pathways might be very important in the pathogenesis of GN. We performed this review to provide a relatively complete signaling pathways flowchart for Nox to the investigators who were interested in the role of Nox in the pathogenesis of GN. Here, we reviewed the signal transduction pathway of Nox and its role in the pathogenesis of GN.     

Toll-like receptors signaling in glomerular diseases

Abstract

Toll-like receptors (TLRs) are pattern-recognition receptors that recognize microbial/vial-derived components that trigger innate immune response, which indicate these molecules play a role in host defense against infection. The infection often precedes numerous disorders including glomerular diseases (glomerulonephritis (GN)). It is reported that TLRs are also involved in the risk and progression of GN, and TLRs may be potential therapeutic targets for GN. To date, a number of studies have found that TLRs are involved in the pathogenesis of GN. There is a paucity of reviews in the literature discussing signaling pathways and gene expression for TLRs in GN. This review was performed to provide a relatively complete signaling pathway flowchart for TLRs to the investigators who were interested in the roles of TLRs in the pathogenesis of GN. In the past decades, some studies were also performed to explore the association of TLRs gene expression with the risk of GN. However, the role of TLRs in the pathogenesis of GN remains controversial. Here, the signal transduction pathways of TLRs and its role of gene expression in the pathogenesis of GN were reviewed.     

The signaling pathway of uromodulin and its role in kidney diseases

Abstract

The uromodulin (UMOD) is a glycoprotein expressed exclusively by renal tubular cells lining the thick ascending limb of the loop of Henle. UMOD acts as a regulatory protein in health and in various conditions. For kidney diseases, its role remains elusive. On one hand, UMOD plays a role in binding and excretion of various potentially injurious products from the tubular fluid. On the other hand, chronic kidney disease is associated with higher serum levels of UMOD. Signaling pathways might be very important in the pathogenesis of kidney diseases. We performed this review to provide a relatively complete signaling pathway flowchart for UMOD to the investigators who were interested in the role of UMOD in the pathogenesis of kidney diseases. Here, we reviewed the signal transduction pathway of UMOD and its role in the pathogenesis of kidney diseases.     

Role of miR-107 and its signaling pathways in diseases

Abstract

MicroRNAs exert their biologic effects by targeting specific mRNAs for degradation or translational inhibition. MicroRNA-mediated regulation is complex, potentially affecting expression of the host gene, related enzymes within the same pathway or apparently distinct targets. miR-107 is found to be implicated in the pathogenesis of some diseases. This review was performed to sum up the role of miR-107 and its signaling pathways in renal diseases.     

Resveratrol and the mitochondria: From triggering the intrinsic apoptotic pathway to inducing mitochondrial biogenesis,a mechanistic view

BackgroundMitochondria, the power plants of the cell, are known as a cross-road of different cellular signaling pathways. These cytoplasmic double-membraned organelles play a pivotal role in energy metabolism and regulate calcium flux in the cells. It is well known that mitochondrial dysfunction is associated with different diseases such as neurodegeneration and cancer. A growing body of literature has shown that polyphenolic compounds exert direct effects on mitochondrial ultra-structure and function. Resveratrol is known as one of the most common bioactive constituents of red wine, which improves mitochondrial functions under in vitro and in vivo conditions.Scope of reviewThis paper aims to review the molecular pathways underlying the beneficial effects of resveratrol on mitochondrial structure and functions. In addition, we discuss the chemistry and main sources of resveratrol.Major conclusionsResveratrol represents the promising effects on mitochondria in different experimental models. However, there are several reports on the detrimental effects elicited by resveratrol on mitochondria.General significanceAn understanding of the chemistry and source of resveratrol, its bioavailability and the promising effects on mitochondria brings a new hope to therapy of mitochondrial dysfunction-related diseases.     

Role of microRNA-155 in autoimmunity

MicroRNAs (miRNAs) have recently emerged as a major class of gene expression regulators linked to most biological functions. MiR-155 is encoded within a region known as B cell integration cluster (Bic) gene, identified originally as a frequent integration site for the avian leukosis virus. Disregulation of endogenous miR-155 has been implicated in the pathogenesis of human cancers. Recently, aberrant expression of miR-155 was observed in many autoimmune conditions, including rheumatoid arthritis (RA), multiple sclerosis (MS), and systemic lupus erythematosus (SLE). Moreover, functional analysis demonstrated that miR-155 has powerful regulatory potential in a wide variety of immune cells through targeting specific mRNAs. Since pathogenic immune cells play a pivotal role in pathogenesis of human autoimmune diseases, miR-155 might be a versatile therapeutic target. This review will discuss the current understandings for the role of miR-155 in autoimmunity.     

Signaling pathway factors expression in renal tissue of apoE-knockout mice

Abstract

Apolipoprotein E (apoE) is regarded as one of the major plasma lipoproteins, and it plays an important role in the transport and metabolism of lipids. apoE can be found in multiple tissues, such as liver, kidney, jejunum, urinary bladder, ileum, colon, brain, adrenal glands, lung, ovary, spleen, pancreas, and testis, etc. As a secreted protein, it plays an important role in the systemic lipoprotein metabolism and vascular wall homeostasis and in the pathogenesis of renal diseases. apoE-knockout (apoE(?/?)) mice is a classic model of atherosclerosis and renal diseases. However, no review summed up the signaling pathway factors expression in renal tissue of apoE-knockout mice. The literatures were searched extensively and this review was performed to review the signaling pathway factors expression in renal tissue of apoE-knockout mice.     

The signaling pathway of hypoxia inducible factor and its role in renal diseases

Abstract

It is well-documented that hypoxia inducible factor (HIF) is a key mediator of tissue and cellular adaptation to hypoxia. HIF-target genes are also involved in cellular apoptosis and profibrotic mechanisms. The role of HIF in diseases is not consistent. It is a risk factor for tumor progression, whereas it plays a protective role against ischemic hypofusion. For renal diseases, it is not always a risk or protective factor. Many factors are involved in the pathogenesis of renal diseases. It is reported that HIF not only increases hypoxia tolerance, but also regulates a lot of signaling pathways. In the past decades, a number of studies were also conducted to explore the association between HIF and the risk of renal diseases. However, the role of HIF in the development of renal diseases was not entirely clear. In this study, the signal transduction pathways of HIF and its role in the pathogenesis of renal diseases were reviewed.     

Role of miR-21 and its signaling pathways in renal diseases

Abstract

miRNAs are endogenous non-coding RNAs that are ～22 nucleotides in length and can have structural, enzymatic and regulatory functions. miRNAs play important roles in the progression of renal fibrosis. miR-21, through a feed-forward loop and a downstream mediator of transforming growth factor-β (TGF-β), amplifies TGF-β signaling and promotes fibrosis. miR-21 is high on the list of non-coding, small, regulatory RNAs that promote renal fibrosis and emerges as a serum biomarker for kidney diseases, but many questions await answers. This review was performed to sum up the role of miR-21 and its signaling pathways in renal diseases.     

Mitogen-activated protein kinases as key players in osmotic stress signaling

BackgroundOsmotic stress arises from the difference between intracellular and extracellular osmolality. It induces cell swelling or shrinkage as a consequence of water influx or efflux, which threatens cellular activities. Mitogen-activated protein kinases (MAPKs) play central roles in signaling pathways in osmotic stress responses, including the regulation of intracellular levels of inorganic ions and organic osmolytes.Scope of reviewThe present review summarizes the cellular osmotic stress response and the function and regulation of the vertebrate MAPK signaling pathways involved. We also describe recent findings regarding apoptosis signal-regulating kinase 3 (ASK3), a MAP3K member, to demonstrate its regulatory effects on signaling molecules beyond MAPKs.Major conclusionsMAPKs are rapidly activated by osmotic stress and have diverse roles, such as cell volume regulation, gene expression, and cell survival/death. There is significant cell type specificity in the function and regulation of MAPKs. Based on its activity change during osmotic stress and its regulation of the WNK1-SPAK/OSR1 pathway, ASK3 is expected to play important roles in osmosensing mechanisms and cellular functions related to osmoregulation.General significanceMAPKs are essential for various cellular responses to osmotic stress; thus, the identification of the upstream regulators of MAPK pathways will provide valuable clues regarding the cellular osmosensing mechanism, which remains elusive in mammals. The elucidation of in vivo MAPK functions is also important because osmotic stress in physiological and pathophysiological conditions often results from changes in the intracellular osmolality. These studies potentially contribute to the establishment of therapeutic strategies against diseases that accompany osmotic perturbation.     

PINCH: More than just an adaptor protein in cellular response

Particularly interesting new cysteine‐histidine‐rich protein (PINCH) is a LIM‐domain‐only adaptor protein involved in protein recruitment, subsequent assembly of multi‐protein complexes, and subcellular localization of these complexes. PINCH is developmentally regulated and its expression is critical for proper cytoskeletal organization and extracellular matrix adhesion. Although PINCH has no catalytic abilities, the PIP (PINCH–ILK–parvin) complex serves as a link between integrins and components of growth factor receptor kinase and GTPase signaling pathways. Accordingly, PINCH‐mediated signaling induces cell migration, spreading, and survival. Further research on the signaling cascades affected by PINCH is key to appreciating its biological significance in cell fate and systems maintenance, as the developmental functions of PINCH may extend to disease states and the cellular response to damage. PINCH is implicated in a diverse array of diseases including renal failure, cardiomyopathy, nervous system degeneration and demyelination, and tumorigenesis. This review presents evidence for PINCH's structural and functional importance in normal cellular processes and in pathogenesis. The current data for PINCH expression in nervous system disease is substantial, but due to the complex and ubiquitous nature of this protein, our understanding of its function in pathology remains unclear. In this review, an overview of studies identifying PINCH binding partners, their molecular interactions, and the potentially overlapping role(s) of PINCH in cancer and in nervous system diseases will be discussed. Many questions remain regarding PINCH's role in cells. What induces cell‐specific PINCH expression? How does PINCH expression contribute to cell fate in the central nervous system? More broadly, is PINCH expression in disease a good thing? Clarifying the ambiguous functions of PINCH expression in the central nervous system and other systems is important to understand more clearly signaling events both in health and disease. J. Cell. Physiol. 226: 940–947, 2011. © 2010 Wiley‐Liss, Inc.     

Clinical application of quantitative glycomics

ABSTRACT

Introduction: Aberrant glycosylation has been associated with many diseases. Decades of research activities have reported many reliable glycan biomarkers of different diseases which enable effective disease diagnostics and prognostics. However, none of the glycan markers have been approved for clinical diagnosis. Thus, a review of these studies is needed to guide the successful clinical translation.

Area covered: In this review, we describe and discuss advances in analytical methods enabling clinical glycan biomarker discovery, focusing only on studies of released glycans. This review also summarizes the different glycobiomarkers identified for cancers, Alzheimer’s disease, diabetes, hepatitis B and C, and other diseases.

Expert commentary: Along with the development of techniques in quantitative glycomics, more glycans or glycan patterns have been reported as better potential biomarkers of different diseases and proved to have greater diagnostic/diagnostic sensitivity and specificity than existing markers. However, to successfully apply glycan markers in clinical diagnosis, more studies and verifications on large biological cohorts need to be performed. In addition, faster and more efficient glycomic strategies need to be developed to shorten the turnaround time. Thus, glycan biomarkers have an immense chance to be used in clinical prognosis and diagnosis of many diseases in the near future.     

Metabolic utilization and remodeling of glycan biosynthesis using fucose analogs

BackgroundFucose (Fuc), a monosaccharide present at the core or the termini of glycans, critically regulates various biological phenomena and is associated with various diseases. Specifically detecting Fuc residues or inhibiting the fucosylation pathway is pivotal in understanding the mechanisms of how fucosylated glycans are related to biological processes and diseases and in developing novel therapeutic agents.Scope of reviewThis review focuses on chemical biology approaches using Fuc analogs developed for metabolically labeling fucosylated glycans or inhibiting the biosynthesis of fucosylated glycans.Major conclusionsDeveloped Fuc analogs have different potency, specificity and effects on protein and cellular functions. Developing highly enzyme-specific probes and inhibitors is desirable for future investigations.General significanceChemical glycobiology approaches using sugar analogs are useful for revealing novel mechanisms of inter-relationships among sugar metabolism pathways and manipulating glycan expression to develop new glycan-targeted therapies.     

Glycation-induced modification of tissue-specific ECM proteins: A pathophysiological mechanism in degenerative diseases

BackgroundGlycation driven generation of advanced glycation end products (AGEs) and their patho-physiological role in human degenerative diseases has remained one of the thrust areas in the mainstream of disease biology. Glycation of extracellular matrix (ECM) proteins have deleterious effect on the mechanical and functional properties of tissues. Owing to the adverse pathophysiological concerns of glycation, there is a need to decipher the underlying mechanisms.Scope of reviewAGE-modified ECM proteins affect the cell in the vicinity by altering protein structure-function, matrix-matrix or matrix-cell interaction and by activating signalling pathway through receptor for AGE. This review is intended for addressing the AGE-induced modification of tissue-specific ECM proteins and its implication in the pathogenesis of various organ-specific human ailments.Major conclusionsThe glycation affects the canonical cell behaviour due to alteration in the interaction of glycated ECM with receptors like integrins and discodin domain, and the signalling cues generated subsequently affect the downstream signalling pathways. Consequently, the variation of structural and functional properties of tissues due to matrix glycation helps in the initiation or progression of the disease condition.General significanceThis review offers comprehensive knowledge about the remodelling of glycation induced ECM and tissue-specific pathological concerns. As glycation of ECM affects the normal tissues and cell behaviour, the scientific discourse may also provide cues for developing candidate drugs that may help in attenuating the adverse effects of AGEs and perhaps open a research window of tailoring novel strategies for the management of glycation induced human degenerative diseases.     

Characterization of novel anti-IL-26 neutralizing monoclonal antibodies for the treatment of inflammatory diseases including psoriasis

ABSTRACT

Interleukin (IL)-26, known as a Th17 cytokine, acts on various cell types and has multiple biological functions. Although its precise role still remains to be elucidated, IL-26 is suggested to be associated with the pathology of diverse chronic inflammatory diseases such as psoriasis, inflammatory bowel diseases and rheumatoid arthritis. To develop novel neutralizing anti-human IL-26 monoclonal antibodies (mAbs) for therapeutic use in the clinical setting, we immunized mice with human IL-26 protein. Hybridomas producing anti-IL-26 mAbs were screened for various in vitro functional assays, STAT3 phosphorylation and antibiotic assays. Although the IL-20RA/IL-10RB heterodimer is generally believed to be the IL-26 receptor, our data strongly suggest that both IL-20RA-dependent and -independent pathways are involved in IL-26-mediated stimulation. We also investigated the potential therapeutic effect of anti-IL-26 mAbs in the imiquimod-induced psoriasis-like murine model using human IL-26 transgenic mice. These screening methods enabled us to develop novel neutralizing anti-human IL-26 mAbs. Importantly, administration of IL-26-neutralizing mAb did not have an effect on the antimicrobial activity of IL-26. Taken together, our data strongly suggest that our newly developed anti-human IL-26 mAb is a potential therapeutic agent for the treatment of diverse chronic inflammatory diseases including psoriasis.     

MiRNA-664在肿瘤中的研究进展

近年来,研究者在肿瘤发生发展的相关研究中发现,microRNA-664(miR-664)很可能是一个在肿瘤发展进程中发挥重要作用的miRNA。和肿瘤周围的正常组织相比,在不同的肿瘤组织中,miR-664的表达水平有些出现升高,有些出现降低,因此,其在不同肿瘤中发挥的生物学功能也不尽相同。相关研究证实,miR-664可影响细胞的增殖、周期调控、再生等过程,而其在代谢、凋亡和自噬等生物学功能中发挥何种作用仍需进一步深入探究。更加系统的深入研究miR-664将有助于发掘其在基因靶向诊断与治疗领域中的应用。