title: Adiponectin promotes functional recovery after podocyte ablation.
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.
authors: Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Joseph M
authors: JM
authors: Rutkowski
authors: Zhao V
authors: ZV
authors: Wang
authors: Ae Seo Deok
authors: AS
authors: Park
authors: Jianning
authors: J
authors: Zhang
authors: Dihua
authors: D
authors: Zhang
authors: Ming Chang
authors: MC
authors: Hu
authors: Orson W
authors: OW
authors: Moe
authors: Katalin
authors: K
authors: Susztak
authors: Philipp E
authors: PE
authors: Scherer
mesh_terms: D000085:Acetates / Q000494:pharmacology; D052242:Adiponectin / Q000235:genetics / Q000494:pharmacology*; D000419:Albuminuria / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005355:Fibrosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D060730:Glomerular Filtration Barrier / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D047495:PPAR gamma / Q000037:antagonists & inhibitors; D050199:Podocytes / Q000473:pathology / Q000502:physiology*; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology*; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: C483845:2-(2-(4-phenoxy-2-propylphenoxy)ethyl)indole-5-acetic acid; D000085:Acetates; D052242:Adiponectin; C499919:Adipoq protein, mouse; D007211:Indoles; D047495:PPAR gamma; C505409:Casp3 protein, mouse; C505526:Casp8 protein, mouse; D053148:Caspase 3; D053181:Caspase 8