Dataset related to article "C3a receptor blockade protects podocytes from injury in diabetic nephropathy"

<em>The file contains raw data related to the article "C3a receptor blockade protects podocytes from injury in diabetic nephropathy", available from https://insight.jci.org/articles/view/131849.</em> <strong>Raw data vivo 1</strong>: evaluations of complement protein renal expression in vivo <strong>Raw data vivo 2</strong>: evaluations of systemic and laboratory parameters in vivo <strong>Raw data vivo 3</strong>: histological evaluation of glomerular damage in vivo <strong>Raw data vivo 4</strong>: histological evaluation of podocyte and mitochondrial dysfunction in vivo <strong>Raw data vitro 1</strong>: evaluations of mitochondrial functional integrity in cultured podocytes <strong>Raw data vitro 2</strong>: western blot analyses of mitochondrial proteins in cultured podocytes <strong>Raw data vitro 3</strong>: evaluations of mitochondrial bioenergetic changes in cultured podocytes <strong>Raw data vitro 4</strong>: evaluations of the effect of SS-31 in cultured podocytes <strong>Abstract of the manuscript</strong>: Renal activation of the complement system has been described in patients with diabetic nephropathy (DN), although its pathological relevance is still ill-defined. Here, we studied whether glomerular C3a, generated by uncontrolled complement activation, promotes podocyte damage, leading to proteinuria and renal injury in mice with type 2 diabetes. BTBR ob/ob mice exhibited podocyte loss, albuminuria, and glomerular injury accompanied by C3 deposits and increased C3a and C3a receptor (C3aR) levels. Decreased glomerular nephrin and α-actinin4 expression, coupled with integrin-linked kinase induction, were also observed. Treatment of DN mice with a C3aR antagonist enhanced podocyte density and preserved their phenotype, limiting proteinuria and glomerular injury. Mechanistically, ultrastructural and functional mitochondrial alterations, accompanied by downregulation of antioxidant superoxide dismutase 2 (SOD2) and increased protein oxidation, occurred in podocytes and were normalized by C3aR blockade. In cultured podocytes, C3a induced cAMP-dependent mitochondrial fragmentation. Alterations of mitochondrial membrane potential, SOD2 expression, and energetic metabolism were also found in response to C3a. Notably, C3a-induced podocyte motility was inhibited by SS-31, a peptide with mitochondrial protective effects. These data indicate that C3a blockade represents a potentially novel therapeutic strategy in DN for preserving podocyte integrity through the maintenance of mitochondrial functions.