Matrix metalloproteinase 9 induces keratinocyte apoptosis through FasL/Fas pathway in diabetic wound. 2019

Ying Liang, and Chuan Yang, and Yongqing Lin, and Yasir Parviz, and Kan Sun, and Wei Wang, and Meng Ren, and Li Yan
Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou, 510120, Guangdong, China.

Apoptosis is a mechanism to remove unwanted cells in the tissue. In diabetic wound, which is characterized by delayed healing process, excessive apoptosis is documented and plays a crucial role. Matrix metalloproteinase 9 (MMP9), which is elevated in non-healed diabetic wound, is necessary for healing process but its abnormality resulted in a delayed healing. The classical function of MMP9 is the degradation of extracellular matrix (ECM). However, there is some literature evidence that MMP9 triggers cell apoptosis. Whether the excessive MMP9 contributes to epidermis cell apoptosis in delayed healing diabetic wound and the underlying mechanisms is not clear. In this study, we aimed to explore whether MMP9 induced keratinocyte apoptosis and investigate the plausible mechanisms. Our in vitro study showed that advanced glycation end products (AGEs) induced keratinocyte apoptosis and enhanced MMP9 level. Besides, MMP9, both intra-cellular expressions and extra-cellular supplement, promoted cell apoptosis. Further, MMP9 resulted in an increased expression of FasL, other than Fas and p53. These findings identified a novel effect that MMP9 exerted in delayed diabetic wound healing, owing to a pro-apoptotic effect on keratinocyte, which was mediated by an increase of FasL expression. This study increases understanding of elevated MMP9 which is involved in diabetic wound repair and offers some insights into novel future therapies.

UI MeSH Term Description Entries
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012710 Serum Albumin, Bovine Serum albumin from cows, commonly used in in vitro biological studies. (From Stedman, 25th ed) Fetal Bovine Serum,Fetal Calf Serum,Albumin Bovine,Bovine Albumin,Bovine Serum Albumin,Albumin, Bovine,Albumin, Bovine Serum,Bovine Serum, Fetal,Bovine, Albumin,Calf Serum, Fetal,Serum, Fetal Bovine,Serum, Fetal Calf
D014945 Wound Healing Restoration of integrity to traumatized tissue. Healing, Wound,Healings, Wound,Wound Healings
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015603 Keratinocytes Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. Keratinocyte
D017127 Glycation End Products, Advanced A heterogeneous group of compounds derived from rearrangements, oxidation, and cross-linking reactions that follow from non-enzymatic glycation of amino groups in PROTEINS; LIPIDS; or NUCLEIC ACIDS. Their accumulation in vivo accelerates under hyperglycemic, oxidative, or inflammatory conditions. Heat also accelerates the formation of advanced glycation end products (AGEs) such seen with the browning of food during cooking. Advanced Glycation End Product,Advanced Glycation Endproduct,Advanced Maillard Reaction End Product,Glycated Lipids,Glycotoxins,Maillard Product,Maillard Reaction End Product,Maillard Reaction Product,Advanced Glycation End Products,Advanced Glycation Endproducts,Advanced Maillard Reaction End Products,Glycation Endproducts, Advanced,Maillard Products,Maillard Reaction End Products,Maillard Reaction Products,Glycation Endproduct, Advanced,Lipids, Glycated,Product, Maillard Reaction,Products, Maillard,Products, Maillard Reaction,Reaction Products, Maillard
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D017719 Diabetic Foot Common foot problems in persons with DIABETES MELLITUS, caused by any combination of factors such as DIABETIC NEUROPATHIES; PERIPHERAL VASCULAR DISEASES; and INFECTION. With the loss of sensation and poor circulation, injuries and infections often lead to severe foot ulceration, GANGRENE and AMPUTATION, SURGICAL. Foot Ulcer, Diabetic,Diabetic Feet,Feet, Diabetic,Foot, Diabetic
D053222 Fas Ligand Protein A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS. Antigens, CD178,CD178 Antigens,Tumor Necrosis Factor Ligand Superfamily Member 6,CD178 Antigen,CD95 Antigen Ligand,CD95 Ligand,CD95L,Fas Ligand,Fas Ligand (FasL),FasL Protein,TNF Superfamily, Member 6,Antigen, CD178

Related Publications

Ying Liang, and Chuan Yang, and Yongqing Lin, and Yasir Parviz, and Kan Sun, and Wei Wang, and Meng Ren, and Li Yan
May 2004, Environmental toxicology and pharmacology,
Ying Liang, and Chuan Yang, and Yongqing Lin, and Yasir Parviz, and Kan Sun, and Wei Wang, and Meng Ren, and Li Yan
September 2011, Archives of toxicology,
Ying Liang, and Chuan Yang, and Yongqing Lin, and Yasir Parviz, and Kan Sun, and Wei Wang, and Meng Ren, and Li Yan
January 2008, Journal of cellular physiology,
Ying Liang, and Chuan Yang, and Yongqing Lin, and Yasir Parviz, and Kan Sun, and Wei Wang, and Meng Ren, and Li Yan
December 2011, Molecular and cellular biochemistry,
Ying Liang, and Chuan Yang, and Yongqing Lin, and Yasir Parviz, and Kan Sun, and Wei Wang, and Meng Ren, and Li Yan
December 2017, Environmental toxicology and pharmacology,
Ying Liang, and Chuan Yang, and Yongqing Lin, and Yasir Parviz, and Kan Sun, and Wei Wang, and Meng Ren, and Li Yan
October 2004, Bulletin of environmental contamination and toxicology,
Ying Liang, and Chuan Yang, and Yongqing Lin, and Yasir Parviz, and Kan Sun, and Wei Wang, and Meng Ren, and Li Yan
March 2009, Environmental toxicology and pharmacology,
Ying Liang, and Chuan Yang, and Yongqing Lin, and Yasir Parviz, and Kan Sun, and Wei Wang, and Meng Ren, and Li Yan
July 2012, Respiratory physiology & neurobiology,
Ying Liang, and Chuan Yang, and Yongqing Lin, and Yasir Parviz, and Kan Sun, and Wei Wang, and Meng Ren, and Li Yan
June 2006, Methods and findings in experimental and clinical pharmacology,
Ying Liang, and Chuan Yang, and Yongqing Lin, and Yasir Parviz, and Kan Sun, and Wei Wang, and Meng Ren, and Li Yan
January 2005, Journal of receptor and signal transduction research,
Copied contents to your clipboard!