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

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.

• Raw data vivo 1: evaluations of complement protein renal expression in vivo
• Raw data vivo 2: evaluations of systemic and laboratory parameters in vivo
• Raw data vivo 3: histological evaluation of glomerular damage in vivo
• Raw data vivo 4: histological evaluation of podocyte and mitochondrial dysfunction in vivo
• Raw data vitro 1: evaluations of mitochondrial functional integrity in cultured podocytes
• Raw data vitro 2: western blot analyses of mitochondrial proteins in cultured podocytes
• Raw data vitro 3: evaluations of mitochondrial bioenergetic changes in cultured podocytes
• Raw data vitro 4: evaluations of the effect of SS-31 in cultured podocytes

Abstract of the manuscript:

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.