PMID- 29096559 OWN - NLM STAT- MEDLINE DCOM- 20180705 LR - 20231213 IS - 1029-2470 (Electronic) IS - 1029-2470 (Linking) VI - 51 IP - 11-12 DP - 2017 Dec TI - Retinoic acid receptors alpha and gamma are involved in antioxidative protection in renal tubular epithelial cells injury induced by hypoxia/reoxygenation. PG - 873-885 LID - 10.1080/10715762.2017.1387655 [doi] AB - Renal interstitial fibrosis (RIF) is a common outcome in various chronic kidney diseases. Injury to renal tubular epithelial cell (RTEC) is major link in RIF. Hypoxia is one of the common factors for RTEC damage. Retinoic acid receptors (RARs), RARalpha, RARbeta and RARgamma, are evolutionary conserved and pleiotropic proteins that have been involved in various cellular functions, including proliferation, differentiation, apoptosis, and transcription. Recently, we discovered that aberrant expression of RARs was involved in the development of RIF in rats. Here, we investigated the role of RARs in the hypoxia/reoxygenation (HR) damage model in RTEC with virus-based delivery vectors to knockdown or overexpress RARs. Relevant indicators were detected. Our results showed that HR inhibited RARalpha and RARgamma expressions in a time-dependent manner in RTECs; however, the expression of RARbeta was not changed obviously. RARalpha and RARgamma overexpression could protect cells from oxidative stress-induced injury by inhibiting HR-induced intracellular superoxide anion (O(2)(-)) generation, cell viability and mitochondria membrane potential (MMP) decrease and transforming growth factor beta1 (TGF-beta1) expression and promoting endogenous antioxidant defense components, superoxide dismutase (SOD) and glutathione (GSH). Meanwhile, inhibition of RARalpha and RARgamma expressions by small interference RNAs (siRNA) resulted in a less resistance of RTEC to HR as shown in increased O(2)(-) production and TGF-beta1 expression and decreased cell viability, MMP, SOD and GSH levels. These data indicates that RARalpha and RARgamma act as positive regulators to offset oxidative damage and profibrosis cytokine accumulation and therefore has an antioxidative effect. FAU - Jiang, Ling AU - Jiang L AD - a Department of Pediatrics , The First Affiliated Hospital of Guangxi Medical University , Nanning , PR China. FAU - Qin, Yuanhan AU - Qin Y AD - a Department of Pediatrics , The First Affiliated Hospital of Guangxi Medical University , Nanning , PR China. FAU - Lei, Fengying AU - Lei F AD - a Department of Pediatrics , The First Affiliated Hospital of Guangxi Medical University , Nanning , PR China. FAU - Chen, Xiuping AU - Chen X AD - a Department of Pediatrics , The First Affiliated Hospital of Guangxi Medical University , Nanning , PR China. FAU - Zhou, Zhiqiang AU - Zhou Z AD - a Department of Pediatrics , The First Affiliated Hospital of Guangxi Medical University , Nanning , PR China. LA - eng PT - Journal Article DEP - 20171103 PL - England TA - Free Radic Res JT - Free radical research JID - 9423872 RN - 0 (Antioxidants) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Retinoic Acid Receptor alpha) SB - IM MH - Animals MH - Antioxidants/*metabolism MH - Cell Hypoxia/*physiology MH - Epithelial Cells/*metabolism/pathology MH - Kidney Diseases/*etiology/metabolism MH - Male MH - Rats MH - Receptors, Retinoic Acid/*metabolism MH - Retinoic Acid Receptor alpha/*metabolism MH - Retinoic Acid Receptor gamma OTO - NOTNLM OT - Hypoxia/reoxygenation OT - oxidative stress OT - renal interstitial fibrosis OT - renal tubular epithelial cells OT - retinoic acid receptors EDAT- 2017/11/04 06:00 MHDA- 2018/07/06 06:00 CRDT- 2017/11/04 06:00 PHST- 2017/11/04 06:00 [pubmed] PHST- 2018/07/06 06:00 [medline] PHST- 2017/11/04 06:00 [entrez] AID - 10.1080/10715762.2017.1387655 [doi] PST - ppublish SO - Free Radic Res. 2017 Dec;51(11-12):873-885. doi: 10.1080/10715762.2017.1387655. Epub 2017 Nov 3.