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High glucose increases extracellular matrix production in pancreatic stellate cells by activating the renin–angiotensin system
Author(s) -
Ko SeungHyun,
Hong OakKee,
Kim JiWon,
Ahn YuBai,
Song KiHo,
Cha BongYun,
Son HoYoung,
Kim MyungJun,
Jeong InKyung,
Yoon KunHo
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20797
Subject(s) - candesartan , ctgf , medicine , endocrinology , hepatic stellate cell , angiotensin ii , chemistry , extracellular matrix , growth factor , renin–angiotensin system , receptor , fibrosis , angiotensin converting enzyme , biology , biochemistry , blood pressure
Pancreatic stellate cells (PSCs) are involved in pancreatic inflammation and fibrosis. Recent studies have shown that blocking the renin–angiotensin system (RAS) attenuates pancreatic inflammation and fibrosis. However, there are few data about the direct effects of high glucose on extracellular matrix (ECM) protein synthesis and angiotensin II (Ang II) induction in PSCs. PSCs were isolated from male Sprague–Dawley rats and cultured in medium containing 5.5 mM (LG group) or 27 mM D ‐glucose (HG group). Levels of Ang II and transforming growth factor‐β (TGF‐β) in culture media were measured and Ang II‐positive cells were counted. We used real‐time polymerase chain reaction (PCR) to detect Ang II receptor expression and Western blot analysis for the expression of ECM proteins such as connective‐tissue growth factor (CTGF) and collagen type IV. Cells were also treated with an Ang II‐receptor antagonist (candesartan, 10 µM) or angiotensin‐converting enzyme (ACE) inhibitor (ramiprilat, 100 nM). Thymidine uptake by PSCs increased fourfold with high glucose treatment. Ang II levels and the proportion of Ang II‐positive PSCs were significantly increased after 6 h under high‐glucose conditions. TGF‐β concentrations also increased significantly with high glucose. After 72 h, the expression of CTGF and collagen type IV proteins in high‐glucose cultures increased significantly and this increase was effectively attenuated by the candesartan or the ramiprilat. All together, high glucose induced PSCs proliferation and ECM protein synthesis, and these effects were attenuated by an Ang II‐receptor antagonist. The data suggest that pancreatic inflammation and fibrosis aggravated by hyperglycemia, and Ang II play an important role in this pathogenesis. J. Cell. Biochem. 98: 343–355, 2006. © 2006 Wiley‐Liss, Inc.