Adiponectin Promotes Functional Recovery after Podocyte... : Journal of the American Society of Nephrology (original) (raw)

Basic Research

Rutkowski, Joseph M.*; Wang, Zhao V.*; Park, Ae Seo Deok†; Zhang, Jianning‡; Zhang, Dihua‡,§; Hu, Ming Chang§,‡; Moe, Orson W.‡,§,¶; Susztak, Katalin†; Scherer, Philipp E.*,‡,**

*Touchstone Diabetes Center,

‡Department of Internal Medicine,

¶Department of Physiology,

**Department of Cell Biology, and

§Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas, and

†Renal, Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Correspondence: Dr. Philipp E. Scherer, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard L5.210, Dallas, TX 75390. Email: [email protected]

Received April 24, 2012

Accepted November 13, 2012

Abstract

Low levels of the adipocyte-secreted protein adiponectin correlate with albuminuria in both mice and humans, but whether adiponectin has a causative role in modulating renal disease is unknown. Here, we first generated a mouse model that allows induction of caspase-8–mediated apoptosis specifically in podocytes upon injection of a construct-specific agent. These POD-ATTAC mice exhibited significant kidney damage, mimicking aspects of human renal disease, such as foot process effacement, mesangial expansion, and glomerulosclerosis. After the initial induction, both podocytes and filtration function recovered. Next, we crossed POD-ATTAC mice with mice lacking or overexpressing adiponectin. POD-ATTAC mice lacking adiponectin developed irreversible albuminuria and renal failure; conversely, POD-ATTAC mice overexpressing adiponectin recovered more rapidly and exhibited less interstitial fibrosis. In conclusion, these results suggest that adiponectin is a renoprotective protein after podocyte injury. Furthermore, the POD-ATTAC mouse provides a platform for further studies, allowing precise timing of podocyte injury and regeneration.