Effects of extracellular matrix glycosylation on proliferation and apoptosis of human dermal fibroblasts via the receptor for advanced glycosylated end products.
The balance between proliferation and apoptosis of skin cells is responsible for skin turnover and the success of the wound healing process. Recent reports have shown that advanced glycosylation end product (AGE) formation participates in dermatologic problems in diabetes. However, the effect on proliferation and apoptosis of dermal fibroblasts remains unclear. The aim of this study was to investigate the effects of dermal microenvironment glycosylation on the balance of cellular proliferation and apoptosis. Histology and immunohistochemical staining were performed on type II diabetic and nondiabetic skin tissue specimens to determine the distributions of proliferating cell nuclear antigen, apoptotic cells, AGEs, and receptors for AGEs (RAGEs). Matrix secreted by cultured human fibroblasts was glycosylated by 0.5 M D-ribose. RAGE-blocking antibodies were applied to inhibit the interaction of RAGE and AGEs in this system and then cell viability, cell cycle phase distribution, and apoptosis were measured. Diabetic skin has degenerative, loosely arranged collagen and increased apoptotic cells compared with normal skin. Expression of AGE and RAGE in diabetic skin tissue increased. Glycosylated matrix induced cell cycle arrest and apoptosis of cultured dermal fibroblasts, whereas application of RAGE-blocking antibodies redressed these changes. The accumulation of glycosylated extracellular matrix in diabetic skin tissue is a critical mediator of cellular function. Mediation of RAGE affects the balance of cellular proliferation and apoptosis, which confirms that diabetic wounds possess atypical origin in the repair process.
Niu
Yiwen
Y
Shanghai Burns Institute, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, Peoples' Republic of China.
Xie
Ting
T
Ge
Kui
K
Lin
Yuan
Y
Lu
Shuliang
S
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing / Q000502:physiology
D017127:Glycation End Products, Advanced; D018809:Proliferating Cell Nuclear Antigen; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic