Journal article
RAGE deletion confers renoprotection by reducing responsiveness to transforming growth factor-β and increasing resistance to apoptosis
S Hagiwara, K Sourris, M Ziemann, W Tieqiao, M Mohan, AD McClelland, E Brennan, J Forbes, M Coughlan, B Harcourt, S Penfold, B Wang, G Higgins, R Pickering, A El-Osta, MC Thomas, ME Cooper, P Kantharidis
Diabetes | AMER DIABETES ASSOC | Published : 2018
DOI: 10.2337/db17-0538
Abstract
Signaling via the receptor of advanced glycation end products (RAGE)-though complex and not fully elucidated in the setting of diabetes-is considered a key injurious pathway in the development of diabetic nephropathy (DN). We report here that RAGE deletion resulted in increased expression of fibrotic markers (collagen I and IV, fibronectin) and the inflammatory marker MCP-1 in primary mouse mesangial cells (MCs) and in kidney cortex. RNA sequencing analysis in MCs from RAGE-/- and wild-type mice confirmed these observations. Nevertheless, despite these gene expression changes, decreased responsiveness to transforming growth factor-β was identified in RAGE-/- mice. Furthermore, RAGE deletion ..
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Funding Acknowledgements
S.H. was supported by the Manpei Suzuki Diabetes Foundation. This study was also supported by the Diabetes Australia Research Trust. M.E.C. is supported by the National Health and Medical Research Council. P.K. was supported by the Vera Dalgleish Phillips Fellowship and the National Health and Medical Research Council. This study was also supported in part by the Victorian Government Operational Infrastructure Support Program.