Unravelling reno-protective effects of SGLT2 inhibition in human proximal tubular cells.

Unravelling reno-protective effects of SGLT2 inhibition in human proximal tubular cells. Am J Physiol Renal Physiol. 2018 Dec 12;: Authors: Pirklbauer M, Schupart R, Fuchs LC, Staudinger P, Corazza U, Sallaberger S, Leierer J, Mayer G, Schramek H Abstract Large clinical trials demonstrated that SGLT2 inhibitors (SGLT2i) slow the progression of kidney function decline in type 2 diabetes. As the underlying molecular mechanisms are largely unknown, we studied the effects of SGLT2i on gene expression in two human proximal tubular (PT) cell lines under normoglycemic conditions, utilizing two SGLT2i, namely empagliflocin and canagliflocin. Genome-wide expression analysis did not reveal substantial differences between these two SGLT2i. Microarray hybridization analysis identified 94 genes that were both upregulated by TGF-ß1 and downregulated by either of the two SGLT2i in HK-2 and RPTEC/TERT1 cells. Extracellular matrix organization showed the highest significance in pathway enrichment analysis. Differential gene expression of 3 annotated genes of interest within this pathway was verified on mRNA level in both cell lines: While TGF-ß1 induced mRNA expression of thrombospondin 1 (THBS1) (4,3-fold), tenascin C (TNC) (8-fold) and platelet derived growth factor subunit B (PDGF-B) (4,2-fold), SGLT2i downregulated basal mRNA expression of THBS1 (0,2-fold), TNC (0,5 fold) and PDGF-B (0,6-fold). Administration of SGLT2i in the presence of TGF-ß...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research