Arif Ehtesham, Nihalani Deepak
Department of Medicine, Nephrology Division, Medical University of South Carolina, Charleston, South Carolina, USA.
Nephrology (Carlton). 2019 May;24(5):497-503. doi: 10.1111/nep.13584.
Beta2-adrenergic receptor (β -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 β -AR on disease pathogenesis process was studied, and highlighted the role of β -AR in kidney biology. The expression of β -AR has been noted in many kidney subunits including proximal tubules, glomeruli and podocytes. In vivo studies have shown that in cultured proximal tubules β -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 β -AR activation by short-acting β 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 β agonists restored mitochondrial and renal function in the acute kidney injury mice models through PGC-1α dependent mitochondrial biogenesis. In conclusion, the activation of β -AR may present a rapidly developing therapeutic target for renal diseases.
β2肾上腺素能受体（β-AR）是G蛋白偶联肾上腺素能受体家族成员，其临床意义已在肺部、心血管和肌肉疾病中得到广泛研究，但其在肾脏生物学中的作用仍研究不足。在本综述中，我们讨论了一些近期研究，这些研究探讨了激动剂/拮抗剂介导的β-AR激活/抑制对疾病发病过程的影响，并强调了β-AR在肾脏生物学中的作用。β-AR已在许多肾脏亚单位中被发现，包括近端小管、肾小球和足细胞。体内研究表明，在培养的近端小管中，β-AR通过蛋白激酶-C激活参与Na-ATP酶活性和跨细胞Na转运；而在培养的足细胞中，它与膜去极化有关。动物研究进一步表明，短效β激动剂激活β-AR可通过β-arrestin2依赖的NF-κB失活减轻糖尿病肾病中的单核细胞激活、促炎和促纤维化反应；相反，长效β激动剂激活β-AR可通过PGC-1α依赖的线粒体生物合成恢复急性肾损伤小鼠模型中的线粒体和肾功能。总之，β-AR的激活可能成为肾脏疾病快速发展的治疗靶点。
