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

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)534-541
Number of pages8
JournalNephrology Dialysis Transplantation
Volume23
Issue number2
DOIs
Publication statusPublished - 2008 Feb

All Science Journal Classification (ASJC) codes

  • Nephrology
  • Transplantation

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