Inhibition of SREBP With Fatostatin Does Not Attenuate Early Diabetic Nephropathy in Male Mice

• DOI: 10.1210/en.2018-00093
• Publication Date: 2018-02-05T14:06:25Z
• Authors: Richard Van Krieken; Mandeep Marway; Pavithra Parthasa...; Neel Mehta; Alistar J Ingram; Bo Gao; Joan C Krepinsky
• Keywords: Proinflammatory cytokine; Albuminuria

Sterol regulatory element binding protein (SREBP) is an important potential mediator of kidney fibrosis and known to be upregulated in diabetic nephropathy. We evaluated the effectiveness SREBP inhibition as treatment Type 1 diabetes was induced uninephrectomized male CD1 mice with streptozotocin. The were treated inhibitor fatostatin for 12 weeks. At endpoint, function pathologic findings assessed. Fatostatin inhibited increase both isoforms (types 2) kidneys. Treatment attenuated basement membrane thickening but did not improve hyperfiltration, albuminuria, or mice. nondiabetic led hyperfiltration increased glomerular volume levels seen This associated renal inflammation a trend toward fibrosis. Both vivo cultured proximal tubular epithelial cells, expression proinflammatory cytokine monocyte chemoattractant protein-1. Thus, only ineffective preventing nephropathy also leads injury Further research on efficacy other inhibitors specific roles SREBP-1 SREBP-2 pathogenesis needed.