Role of the β-adrenergic receptor in podocyte injury and recovery.

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 β-adrenergic receptor (β-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 β-AR or if it occurred through "off-target" effects.

METHODS

We genetically deleted the β-AR specifically in murine podocytes and used these mice to determine whether formoterol acting through the podocyte β-AR alone is sufficient for recovery of renal filtration function following injury. The podocyte-specific β-AR knockout mice (β-AR/PodCre) were generated by crossing β-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 β-AR knockout and control mice; however, the β-AR/PodCre mice failed to recover in response to formoterol. Functional evaluation of the β-AR/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 β-AR is a critical component of the recovery mechanism and may serve as a novel therapeutic target for treating podocytopathies.