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In vivo sodium tungstate treatment prevents E‐cadherin loss induced by diabetic serum in HK‐2 cell line
Author(s) -
Bertinat Romina,
Silva Pamela,
Mann Elizabeth,
Li Xuhang,
Nualart Francisco,
Yáñez Alejandro J.
Publication year - 2015
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24974
Subject(s) - medicine , endocrinology , transforming growth factor , diabetic nephropathy , secretion , fibrosis , growth factor , chemistry , kidney , cancer research , biology , receptor
Diabetic nephropathy (DN) is characterized by interstitial inflammation and fibrosis, which is the result of chronic accumulation of extracellular matrix produced by activated fibroblasts in the renal tubulointerstitium. Renal proximal tubular epithelial cells (PTECs), through the process of epithelial‐to‐mesenchymal transition (EMT), are the source of fibroblasts within the interstitial space, and loss of E‐cadherin has shown to be one of the earliest steps in this event. Here, we studied the effect of the anti‐diabetic agent sodium tungstate (NaW) in the loss of E‐cadherin induced by transforming growth factor (TGF) β‐1, the best‐characterized in vitro EMT promoter, and serum from untreated or NaW‐treated diabetic rats in HK‐2 cell line, a model of human kidney PTEC. Our results showed that both TGFβ‐1 and serum from diabetic rat induced a similar reduction in E‐cadherin expression. However, E‐cadherin loss induced by TGFβ‐1 was not reversed by NaW, whereas sera from NaW‐treated rats were able to protect HK‐2 cells. Searching for soluble mediators of NaW effect, we compared secretion of TGFβ isoforms and vascular endothelial growth factor (VEGF)‐A, which have opposite actions on EMT. One millimolar NaW alone reduced secretion of both TGFβ‐1 and ‐2, and stimulated secretion of VEGF‐A after 48 h. However, these patterns of secretion were not observed after diabetic rat serum treatment, suggesting that protection from E‐cadherin loss by serum from NaW‐treated diabetic rats originates from an indirect rather than a direct effect of this salt on HK‐2 cells, via a mechanism independent of TGFβ and VEGF‐A functions. J. Cell. Physiol. 230: 2437–2446, 2015. © 2015 Wiley Periodicals, Inc.