title: The role of TRPC6 in oxidative stress-induced podocyte ischemic injury.
abstract: Increasing evidence suggests that ischemia and hypoxia serve important functions in the development of renal diseases. However, the underlying mechanism of ischemic injury has not been fully understood. In this study, we found that renal ischemia-reperfusion injury induced podocyte effacement and the upregulation of TRPC6 mRNA and protein expression. In in vitro experiments, oxygen glucose deprivation (OGD) treatment enhanced the expression of TRPC6 and TRPC6-dependent Ca(2+) influx. TRPC6 knockdown by siRNA interference attenuated the OGD-induced [Ca(2+)]i and actin assembly. OGD treatment also increased ROS production. Furthermore, inhibition of ROS activity by N-acetyl-l-cysteine (NAC) eliminated the OGD-induced increase in TRPC6 expression and Ca(2+) influx. H2O2 treatment, which results in oxidative stress, also increased TRPC6 expression and Ca(2+) influx. We conclude that TRPC6 upregulation is involved in Ca(2+) signaling and actin reorganization in podocytes after OGD. These findings provide new insight into the mechanisms underlying the cellular response of podocytes to ischemic injury.
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Department of Nephrology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: He
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Emergency, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Liao
authors.affiliation: Department of Nephrology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Meng
authors.affiliation: Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Institute of Nephrology, Harbin Medical University, Harbin, China. Electronic address: jiaojundong@163.com.
authors.forename: Jundong
authors.initials: J
authors.lastname: Jiao
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D050052:TRPC Cation Channels / Q000235:genetics* / Q000378:metabolism; D000074287:TRPC6 Cation Channel; D015854:Up-Regulation
chemical_list: D000199:Actins; D017382:Reactive Oxygen Species; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; C492146:Trpc6 protein, mouse; D005947:Glucose; D010100:Oxygen; D002118:Calcium
keywords: Actin cytoskeleton; OGD; Podocytes; ROS; Renal ischemia-reperfusion injury; TRPC6