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High glucose decreases collagenase expression and increases TIMP expression in cultured human peritoneal mesothelial cells

Authors
 Jin-Ju Kim  ;  Jin-Ji Li  ;  Kyung Sik Kim  ;  Seung-Jae Kwak  ;  Dong-Sub Jung  ;  Dong-Ryeol Ryu  ;  Tae-Hyun Yoo  ;  Hoon Young Choi  ;  Seung Hyeok Han  ;  Hyung Jong Kim  ;  Soo Young Yoon  ;  Dae Suk Han  ;  Shin-Wook Kang 
Citation
 NEPHROLOGY DIALYSIS TRANSPLANTATION, Vol.23(2) : 534-541, 2008 
Journal Title
 NEPHROLOGY DIALYSIS TRANSPLANTATION 
ISSN
 0931-0509 
Issue Date
2008
MeSH
Cells, Cultured ; Collagenases/biosynthesis* ; Collagenases/genetics ; Epithelial Cells/metabolism* ; Fibrillar Collagens/metabolism ; Fibrosis ; Glucose/administration & dosage* ; Humans ; Peritoneum/cytology* ; Peritoneum/pathology* ; RNA, Messenger/biosynthesis ; Tissue Inhibitor of Metalloproteinases/biosynthesis*
Keywords
collagenases ; high glucose ; mesothelial cells ; peritoneal fibrosis ; TIMPs
Abstract
BACKGROUND: Peritoneal fibrosis (PF), a serious problem in long-term continuous ambulatory peritoneal dialysis (CAPD) patients, is characterized by extracellular matrix (ECM) accumulation which results from an imbalance between the synthesis and the degradation of ECM components. Previous studies have demonstrated that ECM synthesis is increased in human peritoneal mesothelial cells (HPMCs) under high glucose conditions, but the effects of high glucose on degradative pathways have not been fully explored. This study was undertaken to elucidate the effects of high glucose on these proteolytic processes in cultured HMPCs. METHODS: HPMCs were isolated from human omentum and were exposed to 5.6 mM glucose (NG), 5.6 mM glucose +34.4 mM mannitol (NG + M), or 40 mM glucose (HG) with or without PKC inhibitor (PKCi). Real-time PCR and western blot were performed to determine collagenases (MMP-1, -8 and -13) and TIMPs (TIMP-1 and -2) mRNA and protein expression, respectively. The individual activities of collagenases in culture media were determined by ELISA. RESULTS: Types I and III collagen protein expression were significantly increased in HG-conditioned media compared to NG media (P < 0.05). The MMP-1, -8 and -13/GAPDH mRNA ratios were significantly lower in HPMCs exposed to HG medium compared to NG cells by 64, 52 and 37%, respectively, and their protein expression by 76, 42 and 49%, respectively, in HG- vs NG-conditioned media. The activities of collagenases in HG-conditioned media were also significantly lower than those in NG media (P < 0.05). In contrast, HG significantly increased TIMPs mRNA ratios and protein expression in HPMCs. These changes in collagenase and TIMP expression induced by HG were abrogated upon pre-treatment with PKCi. CONCLUSION: In conclusion, impaired matrix degradation may contribute to ECM accumulation in PF.
Files in This Item:
T200800155.pdf Download
DOI
10.1093/ndt/gfm553
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Kim, Kyung Sik(김경식) ORCID logo https://orcid.org/0000-0001-9498-284X
Kim, Hyung Jong(김형종)
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Choi, Hoon Young(최훈영) ORCID logo https://orcid.org/0000-0002-4245-0339
Han, Dae Suk(한대석)
Han, Seung Hyeok(한승혁) ORCID logo https://orcid.org/0000-0001-7923-5635
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/106290
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