Beta2-adrenergic receptor in kidney biology: A current prospective

Beta2-adrenergic receptor (β₂ -AR) is a G-protein-coupled adrenergic receptor family member, whose clinical significance has been extensively investigated in lung, cardiovascular and muscular diseases, but its role in kidney biology remains understudied. In this review, we discuss some of the recent studies, where the effect of agonist/antagonist-mediated activation/inhibition of β₂ -AR on disease pathogenesis process was studied, and highlighted the role of β₂ -AR in kidney biology. The expression of β₂ -AR has been noted in many kidney subunits including proximal tubules, glomeruli and podocytes. In vivo studies have shown that in cultured proximal tubules β₂ -AR is involved in Na-ATPase activity and transcellular Na-transport through protein kinase-C activation; whereas in cultured podocytes, it was associated with depolarization of the membrane. The animal studies further revealed that β₂ -AR activation by short-acting β₂ agonists attenuated monocyte activation, pro-inflammatory and pro-fibrotic responses through β-arrestin2 dependent NF-kB inactivation in diabetic kidney disease; in contrast, activation by long-acting β₂ agonists restored mitochondrial and renal function in the acute kidney injury mice models through PGC-1α dependent mitochondrial biogenesis. In conclusion, the activation of β₂ -AR may present a rapidly developing therapeutic target for renal diseases.