Document Detail

Effects of extracellular matrix glycosylation on proliferation and apoptosis of human dermal fibroblasts via the receptor for advanced glycosylated end products.
MedLine Citation:
PMID:  18645306     Owner:  NLM     Status:  MEDLINE    
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.
Yiwen Niu; Ting Xie; Kui Ge; Yuan Lin; Shuliang Lu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American Journal of dermatopathology     Volume:  30     ISSN:  1533-0311     ISO Abbreviation:  Am J Dermatopathol     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-22     Completed Date:  2008-09-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7911005     Medline TA:  Am J Dermatopathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  344-51     Citation Subset:  IM    
Shanghai Burns Institute, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, Peoples' Republic of China.
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MeSH Terms
Apoptosis / physiology*
Blotting, Western
Cell Proliferation*
Cell Survival / physiology
Diabetes Mellitus, Type 2 / metabolism,  pathology
Extracellular Matrix / metabolism*
Fibroblasts / metabolism*,  pathology
Flow Cytometry
Glycosylation End Products, Advanced / metabolism
In Situ Nick-End Labeling
Middle Aged
Proliferating Cell Nuclear Antigen / metabolism
Receptors, Immunologic / metabolism*
Skin / metabolism*,  pathology
Wound Healing / physiology
Reg. No./Substance:
0/Glycosylation End Products, Advanced; 0/Proliferating Cell Nuclear Antigen; 0/Receptors, Immunologic; 0/advanced glycosylation end-product receptor

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