（前）肾素受体[(P)RR]过度激活在促进肾脏纤维化的发生和发展中起着关键作用，但其调控机制尚不清楚。近年研究证实(P)RR的跨膜和胞浆片段是囊泡型H+ -ATP酶（V-ATP酶）的辅助亚基。我们前期研究证实V-ATP酶B2亚基在胞膜表达增强参与了肾脏纤维化过程；并且发现V-ATP酶B2亚基和(P)RR可能存在相互作用，它们作用的增强可能参与了肾脏纤维化进程。本项目拟进一步采用基因切除、点突变等分子生物学技术，证实V-ATP酶B2亚基是否通过与(P)RR的相互作用调控(前)肾素激活后(P)RR胞膜过表达，从而促进TGF-β等促纤维化因子表达；并获取两者相互作用的功能基团和调控机制的可靠证据，以上努力将为丰富V-ATP酶参与和调控肾脏纤维化的功能提供全新的认识，为更有效地阻断肾素血管紧张素系统的病理作用防治肾脏纤维化提供新的靶点。

The (pro)renin receptor ((P)RR) activation plays a key role in the development of renal fibrosis, but the mechanisms is unknown. The transmembrane and cytosolic domain of (P)RR has been shown as accessory subunit of the vacuolar-type H(+)-ATPase (V-ATPase). Our previous study revealed the upregulation of surface expression of B2 subunit of V-ATPase play roles in renal fibrosis. Further study showed that interaction of B2 subunit may have an interaction with (P)RR, which may contribute to renal fibrosis. This study will reveal the role of V-ATPase B2 subunits in regulating overexpression of (P)RR on the plasma membrane activated by (pro)renin, which promotes profibrotic factors (TGF-β)expression. Then this study will further identify the functional domains of B2 and (P)RR that mediate their interaction and the regulated signal pathways. Identification and characterization of these pathways will provide better understanding and noval insights into V-ATPase functioning on renal fibrosis, and help us to provide the new noval candidate targets for preventing renal fibrosis throught reasonable blocking renin-angiotensin system.