看片视频

Sign-up for our newsletter

Publication

Reversibility of structural and functional damage in a model of advanced diabetic nephropathy.

Authors Pichaiwong W, Hudkins KL, Wietecha T, Nguyen TQ, Tachaudomdach C, Li W, Askari B, Kobayashi T, O'Brien KD, Pippin JW, Shankland SJ, Alpers CE Submitted By Charles Alpers on 10/29/2013 Status Published Journal Journal of the American Society of Nephrology : JASN Year 2013 Date Published 6/1/2013 Volume : Pages 24 : 1088 - 1102 PubMed Reference Abstract The reversibility of diabetic nephropathy remains controversial. Here, we tested whether replacing leptin could reverse the advanced diabetic nephropathy modeled by the leptin-deficient BTBR ob/ob mouse. Leptin replacement, but not inhibition of the renin-angiotensin-aldosterone system (RAAS), resulted in near-complete reversal of both structural (mesangial matrix expansion, mesangiolysis, basement membrane thickening, podocyte loss) and functional (proteinuria, accumulation of reactive oxygen species) measures of advanced diabetic nephropathy. Immunohistochemical labeling with the podocyte markers Wilms tumor 1 and p57 identified parietal epithelial cells as a possible source of regenerating podocytes. Thus, the leptin-deficient BTBR ob/ob mouse provides a model of advanced but reversible diabetic nephropathy for further study. These results also suggest that restoration of lost podocytes is possible but is not induced by RAAS inhibition, possibly explaining the limited efficacy of RAAS inhibitors in promoting repair of diabetic nephropathy.

Investigators with authorship
Name Institution Charles Alpers University of Washington Kevin O'Brien University of Washington

Complications
All ComplicationsBioinformatics BoneCardiomyopathy CardiovascularGastro-Intestinal (GI) NephropathyNeuropathy & Neurocognition Pediatric Endocrinology Retinopathy UropathyWound Healing