Interaction between V-ATPase B2 and (Pro) renin Receptors in Promoting the progression of Renal Tubulointerstitial Fibrosis.
To investigate the levels of (Pro) renin receptor [(P) RR], α-smooth muscle actin (α-SMA), fibronectin (FN), and vacuolar H(+)-ATPase (V-ATPase) subunits (B2, E, and c) in rat unilateral ureteral obstruction (UUO) models and rat proximal tubular epithelial cells (NRK-52E) treated with prorenin to elucidate the role of V-ATPase in these processes by activating the (P) RR. UUO significantly upregulated (P) RR, V-ATPase subunits, α-SMA and FN expression in tubulointerstitium or tubular epithelial cells. A marked colocalization of (P) RR and the B2 subunit was also observed. Prorenin treatment upregulated α-SMA, FN, (P) RR, and V-ATPase subunits and activity in NRK52E cell in a dose- and time-dependent manner. The V-ATPase inhibitor bafilomycin A1 partially blocked prorenin-induced (P) RR, FN, and α-SMA expression. Co-immunoprecipitate and immunofluorescence results demonstrated that the V-ATPase B2 subunit bound to the (P) RR, which was upregulated after prorenin stimulation. Either siRNA-mediated (P) RR or B2 subunit knockdown partially reduced V-ATPase activity and attenuated prorenin-induced FN and α-SMA expression. From the data we can assume that activation of (P) RR and V-ATPase may play an important role in tubulointerstitial fibrosis with possible involvement of interaction of V-ATPase B2 subunit and (P)RR.
Department of Nephrology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.|Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
Yun
Y
Liu
Department of Nephrology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.|Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
Sujun
S
Zuo
Department of Nephrology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.|Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
Xiaoyan
X
Li
Department of Nephrology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.|Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
Jinjin
J
Fan
Department of Nephrology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.|Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
Xueqin
X
Cao
Department of Nephrology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.|Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
Xueqing
X
Yu
Department of Nephrology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.|Guangdong Provincial Key Laboratory of Nephrology, Guangzhou 510080, China.
Qiongqiong
Q
Yang
D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis / Q000503:physiopathology*; D009395:Nephritis, Interstitial / Q000503:physiopathology*; D060066:Protein Interaction Maps; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000150:complications*; D000093342:Prorenin Receptor
C503199:Na K ATPase beta2 subunit, rat; D011956:Receptors, Cell Surface; D000254:Sodium-Potassium-Exchanging ATPase; D000093342:Prorenin Receptor