RESUMO
BACKGROUND: Podocytes have a remarkable ability to recover from injury; however, little is known about the recovery mechanisms involved in this process. We recently showed that formoterol, a long-acting ß2-adrenergic receptor (ß2-AR) agonist, induced mitochondrial biogenesis (MB) in podocytes and led to renoprotection in mice. However, it is not clear whether this effect was mediated by formoterol acting through the ß2-AR or if it occurred through "off-target" effects. METHODS: We genetically deleted the ß2-AR specifically in murine podocytes and used these mice to determine whether formoterol acting through the podocyte ß2-AR alone is sufficient for recovery of renal filtration function following injury. The podocyte-specific ß2-AR knockout mice (ß2-ARfl/fl/PodCre) were generated by crossing ß2-AR floxed mice with podocin Cre (B6.Cg-Tg(NPHS2-cre)295Lbh/J) mice. These mice were then subjected to both acute and chronic glomerular injury using nephrotoxic serum (NTS) and adriamycin (ADR), respectively. The extent of injury was evaluated by measuring albuminuria and histological and immunostaining analysis of the murine kidney sections. RESULTS: A similar level of injury was observed in ß2-AR knockout and control mice; however, the ß2-ARfl/fl/PodCre mice failed to recover in response to formoterol. Functional evaluation of the ß2-ARfl/fl/PodCre mice following injury plus formoterol showed similar albuminuria and glomerular injury to control mice that were not treated with formoterol. CONCLUSIONS: These results indicate that the podocyte ß2-AR is a critical component of the recovery mechanism and may serve as a novel therapeutic target for treating podocytopathies.