Adiponectin promotes functional recovery After podocyte ablation

Joseph M. Rutkowski, Zhao Wang, Ae Seo Deok Park, Jianning Zhang, Dihua Zhang, Ming C Hu, Orson W Moe, Katalin Susztak, Philipp E Scherer

Research output: Contribution to journalArticle

76 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)268-282
Number of pages15
JournalJournal of the American Society of Nephrology
Volume24
Issue number2
DOIs
StatePublished - Jan 31 2013

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Podocytes
Adiponectin
Albuminuria
Kidney
Caspase 8
Wounds and Injuries
Adipocytes
Renal Insufficiency
Foot
Regeneration
Proteins
Fibrosis
Apoptosis
Injections

ASJC Scopus subject areas

  • Nephrology

Cite this

Adiponectin promotes functional recovery After podocyte ablation. / Rutkowski, Joseph M.; Wang, Zhao; Park, Ae Seo Deok; Zhang, Jianning; Zhang, Dihua; Hu, Ming C; Moe, Orson W; Susztak, Katalin; Scherer, Philipp E.

In: Journal of the American Society of Nephrology, Vol. 24, No. 2, 31.01.2013, p. 268-282.

Research output: Contribution to journalArticle

Rutkowski, Joseph M. ; Wang, Zhao ; Park, Ae Seo Deok ; Zhang, Jianning ; Zhang, Dihua ; Hu, Ming C ; Moe, Orson W ; Susztak, Katalin ; Scherer, Philipp E. / Adiponectin promotes functional recovery After podocyte ablation. In: Journal of the American Society of Nephrology. 2013 ; Vol. 24, No. 2. pp. 268-282.
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