In vivo sodium tungstate treatment prevents E-cadherin loss induced by diabetic serum in HK-2 cell line.
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.
Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Valdivia, Chile.|Centro de Microscopía Avanzada (CMA)-Bío Bío, Universidad de Concepción, Concepción, Chile.
Romina
R
Bertinat
Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Valdivia, Chile.
Pamela
P
Silva
Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Elizabeth
E
Mann
Division of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Xuhang
X
Li
Centro de Microscopía Avanzada (CMA)-Bío Bío, Universidad de Concepción, Concepción, Chile.
Francisco
F
Nualart
Instituto de Bioquímica y Microbiología, Universidad Austral de Chile, Valdivia, Chile.|Centro de Microscopía Avanzada (CMA)-Bío Bío, Universidad de Concepción, Concepción, Chile.
Alejandro J
AJ
Yáñez
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D017207:Rats, Sprague-Dawley; D017973:Tungsten Compounds / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D015820:Cadherins; D017973:Tungsten Compounds; D042461:Vascular Endothelial Growth Factor A; C025399:sodium tungstate(VI)