title: Suppression of renal TRPM7 may alleviate kidney injury in the renal transplantation.
abstract: OBJECTIVE
  The aim of this study was to investigate the effect of renal cortex transient receptor potential melastatin 7 (TRPM7) suppression on renal ischemia reperfusion injury induced by transplantation in mice.
  
  
  METHODS
  M7shRNA was used to decrease the expression of TRPM7 in NRK-52e cells. The mice were subjected to renal intra-parenchymal injection with lentivirus containing M7shRNA to produce hypo-expression of TRPM7 in renal cortex. Cell hypoxia mode and syngeneic renal transplantation in vivo were established. Then the effects of M7shRNA were measured by fluorescent probe for reactive oxygen species (ROS), intracellular calcium and magnesium; Western blot was applied for p38-MAPKs and Bax expression in cell studies. In vivo studies, mice were killed 24 h, 48 h, 72 h, 7 days and 21 days, respectively, after transplantation and the kidneys were dissected. Serum creatinine was measured, and the H&E, Masson's trichrome staining, TUNEL, Kim-1 and α-smooth muscle actin were used to evaluate pathological change.
  
  
  RESULTS
  In cell model of hypoxia, the level of ROS in NRK-52e-M7shRNA was significantly lower than that in both NRK-52e and NRK-52e control cells, while the activation of p38-MAPKs was limited. In renal transplanted mice, renal function of M7shRNA group was conspicuously better than PBS- and vector-control-treated group. The histological examination showed that renal tubule injury and interstitial fibrosis were lower in M7shRNA-treated group compared with PBS and vector-control group.
  
  
  CONCLUSIONS
  Suppression of renal cortex TRPM7 could alleviate kidney injury induced by transplantation in mice. The mechanism may involve reducing the early stage of ischemia reperfusion injury by inhibition of intracellular Ca(2+), Mg(2+) and ROS.
authors.affiliation: Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China, mengzhe@whu.edu.cn.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Meng
authors.forename: Rui
authors.initials: R
authors.lastname: Cao
authors.forename: Yongzhi
authors.initials: Y
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Cao
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Yang
authors.forename: Xinghuan
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011183:Postoperative Complications / Q000517:prevention & control*; D015427:Reperfusion Injury / Q000517:prevention & control*; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D050053:TRPM Cation Channels; C421903:Trpm7 protein, mouse