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Acute and chronic effects of dietary sodium restriction on renal tubulointerstitial fibrosis in cisplatin-treated rats

Title
Acute and chronic effects of dietary sodium restriction on renal tubulointerstitial fibrosis in cisplatin-treated rats
Author
박준성
Keywords
cisplatin; low-sodium diet; fibrosis; epithelialmesenchymal transition; transforming growth factor
Issue Date
2013-03
Publisher
OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
Citation
NEPHROLOGY DIALYSIS TRANSPLANTATION, 권: 28 호: 3, 페이지: 592-602
Abstract
Renal interstitial fibrosis is a major complication of cisplatin (CP) treatment, and increased sodium intake may accelerate its progression by stimulating transforming growth factor (TGF)-/Smad signaling. However, it is not clear whether a low-sodium diet has beneficial effects on the development of interstitial fibrosis because it activates the reninangiotensinaldosterone system. Here, we tested whether the TGF-/Smad signaling pathway is stimulated in CP-treated rats, and whether the development of tubulointerstitial fibrosis in CP nephropathy can be checked by dietary sodium restriction.Male Sprague Dawley rats were randomly divided into controls, CP treatment and CP treatment with low-sodium diet. The acute experiment lasted 7 days with a single intraperitoneal injection (6 mg/kg) of CP, and the chronic experiment involved weekly injections (2 mg/kg) for 7 weeks.In both sets of experiments, CP treatment produced pronounced tubulointerstitial injury, increased infiltration of ED1-positive cells and increased expression of monocyte chemotactic protein-1 (MCP-1), -smooth muscle actin (SMA), TGF-1, phosphorylated Smad3, fibronectin and collagen III proteins. In the acute experiment, the increases in expression of osteopontin, MCP-1, -SMA, TGF- and collagen III were significantly reduced by dietary sodium restriction. In the chronic experiment, however, none of the measurements were improved by a low-sodium diet. Examination of CP-treated rat kidneys revealed de novo vimentin expression in tubular epithelial cells and invasion of -SMA-positive tubular epithelial cells through the basement membrane into the interstitium.The pro-fibrotic effect of TGF- in CP nephropathy appears to be associated with the epithelialmesenchymal transition and is ameliorated by dietary sodium restriction only during the acute phase.
URI
https://academic.oup.com/ndt/article/28/3/592/1813847http://hdl.handle.net/20.500.11754/44177
ISSN
0931-0509
DOI
10.1093/ndt/gfs496
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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