Angiotensin II Type 2 Receptor Decreases Transforming Growth Factor-beta Type II Receptor Expression and Function in Human Renal Proximal Tubule Cells

作者：Guo, Hui-Lin; Liao, Xiao-Hui; Liu, Qi^*; Zhang, Ling^*

来源：PLos One, 2016, 11(2): e0148696.

DOI：10.1371/journal.pone.0148696

• TO-MESENCHYMAL TRANSITION
• AT(2) RECEPTORS
• BLOOD-PRESSURE
• TGF-BETA-1
• NATRIURESIS
• MECHANISM
• OBESE
• STIMULATION
• INHIBITION
• INCREASES

Transforming growth factor-beta (TGF-beta), via its receptors, induces epithelial-mesenchymal transition (EMT) and plays an important role in the development of renal tubulointersitial fibrosis. Angiotensin II type 2 receptor (AT(2)R), which mediates beneficial renal physiological functions, has received attention as a prospective therapeutic target for renoprotection. In this study, we investigated the effect and underlying mechanism of AT(2)R on the TGF-beta receptor II (TGF-beta RII) expression and function in human proximal tubular cells (HK-2). Here, we show that the AT(2)R agonist CGP42112A decreased TGF-beta RII protein expression in a concentration- and time-dependent manner in HK-2 cells. The inhibitory effect of the AT(2)R on TGF-beta RII expression was blocked by the AT(2)R antagonists PD123319 or PD123177. Stimulation with TGF-beta 1 enhanced EMT in HK-2 cells, which was prevented by pre-treatment with CGP42112A. One of mechanisms in this regulation is associated with the increased TGF-beta RII degradation after activation of AT(2)R. Furthermore, laser confocal immunofluorescence microscopy showed that AT(2)R and TGF-beta RII colocalized in HK-2 cells. AT(2)R and TGF-beta RII coimmunoprecipitated and this interaction was increased after AT(2)R agonist stimulation for 30 min. The inhibitory effect of the AT(2)R on TGF-beta RII expression was also blocked by the nitric oxide synthase inhibitor L-NAME, indicating that nitric oxide is involved in the signaling pathway. Taken together, our study indicates that the renal AT(2)R regulates TGF-beta RII expression and function via the nitric oxide pathway, which may be important in the control of renal tubulointerstitial fibrosis.

• 出版日期2016-2-11
• 单位重庆医科大学