Kidney protection against ischemia/reperfusion injury by myofibrillogenesis regulator-1.
OBJECTIVE
Ischemia/reperfusion (I/R) injury is characterized by cytoskeletal reorganization and loss of polarity in proximal tubule epithelial cells. Previously, we showed that myofibrillogenesis regulator (MR)-1 promoted actin organization in cardiomyocytes. MR-1 is also expressed in the kidney.


METHODS
In this study, we investigated MR-1 expression in acute renal failure induced by I/R in Sprague-Dawley rats. We determined the MR-1 expression and the ratio of fibrous actin (F-actin) to globular actin (G-actin). HK-2 cells were treated with or without hypoxia/reoxygenation (H/R), and MR-1 levels were increased by adenoviral overexpression or silenced by RNA interference.


RESULTS
I/R and H/R resulted in cellular injury and decreases of MR-1, the F-/G-actin ratio, and myosin light chain (MLC)-2. MR-1 overexpression attenuated H/R-induced cell injury and loss of surface membrane polarity of actin. MR-1 overexpression also increased the expression and phosphorylation of MLC-2 and MLC kinase, which were decreased in MR-1-silenced and H/R-treated cells.


CONCLUSIONS
Together, these data show that MR-1 promoted actin polarity on the membrane surface and protected HK-2 cells from H/R injury. The mechanism might involve the rapid organization of F-actin through the upregulation and phosphorylation of MLC-2.
Department of Pathophysiology, PLA General Hospital, Beijing, China.
Xiaoreng
X
Wang
Tianqi
T
Tao
Rui
R
Ding
Dandan
D
Song
Mi
M
Liu
Yuansheng
Y
Xie
Xiuhua
X
Liu
D000199:Actins / Q000378:metabolism*; D058186:Acute Kidney Injury / Q000378:metabolism* / Q000517:prevention & control; D000818:Animals; D024722:Cardiac Myosins / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation; D015316:Genetic Therapy; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control
D000199:Actins; D009124:Muscle Proteins; D018994:Myosin Light Chains; C576747:Pnkd protein, rat; C107184:myosin light chain 2; D009219:Myosin-Light-Chain Kinase; D024722:Cardiac Myosins