The hypoxia-inducible factor-1 alpha (HIF-1 alpha) regulates cellular homeostasis under hypoxic conditions, but it also has pleiotropic effects in response to cellular stresses at normoxia. Here we determined whether HIF-1 alpha has a role in the regulation of mesangial cells in hyperglycemia. In the streptozotocin-induced diabetic mouse model, glomerular mesangial cells had a significant increase in HIF-1 alpha expression in the nucleus. In cultured mesangial

cells, high glucose enhanced the expression of HIF-1 alpha and its target genes known to be involved in the development of diabetic glomerulopathy. A glucose-responsive carbohydrate response element binding protein (ChREBP) was found to have a critical role in the transcriptional upregulation of HIF-1 alpha and downstream gene expression in mesangial cells exposed to high glucose. Knockdown of HIF-1 Cytoskeletal Signaling inhibitor BMS-777607 alpha or ChREBP in mesangial cells abrogated the high glucose-mediated perturbation of gene expression. Our results show that ChREBP and HIF-1 alpha mediate gene regulation in mesangial cells. Further studies will

be needed to find out whether these findings are relevant to the development of the diabetic nephropathy. Kidney International (2010) 78, 48-59; doi: 10.1038/ki.2010.99; published online 7 April 2010″
“Adipokine-producing fatty tissues, composed of preadipocytes, adipocytes, and mesenchymal stem cells, surround the kidney. To study the interaction between renal tubular cells and adipose tissue, we cocultured adipose tissue fragments and MDCK cells. MDCK cells in the coculture showed a taller columnar

shape with improved organization of their microvilli and basal lamina than that seen in MDCK cell monoculture. The adipose tissue-induced change in morphology was replicated when we added leptin to MDCK cells cultured alone. Adiponectin abolished the leptin effect. Adipose tissue selleck chemical fragments inhibited MDCK cell division and also the formation of single-stranded DNA, an indicator of apoptosis. The fragments promoted the expression of polarity-associated proteins, including the tight junction molecules, ZO-1, atypical protein kinase C, and Cdc42. Further, the fragments also accelerated the expression of pendrin, the chloride/iodide transporter in the MDCK cells. In turn, MDCK cells decreased the number of preadipocytes and CD44+/CD105+ mesenchymal stem cells in the fragments, and promoted adiponectin production from the fragments. Thus, our study shows that adipose tissue fragments promote the hypertrophy, polarization, and differentiation of MDCK cells by attenuating their growth and apoptosis through opposing endocrine or paracrine effects of leptin and adiponectin. Further, MDCK cells inhibit the regeneration of preadipocytes and mesenchymal stem cells in adipose tissue.