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Paricalcitol Improves Hypoxia-Induced and TGF-ß1-Induced Injury in Kidney Pericytes.
Lim, Jeong-Hoon; Yook, Ju-Min; Oh, Se-Hyun; Jeon, Soo-Jee; Noh, Hee Won; Jung, Hee-Yeon; Choi, Ji-Young; Cho, Jang-Hee; Kim, Chan-Duck; Kim, Yong-Lim; Park, Sun-Hee.
Afiliación
  • Lim JH; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.
  • Yook JM; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.
  • Oh SH; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.
  • Jeon SJ; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.
  • Noh HW; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.
  • Jung HY; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.
  • Choi JY; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.
  • Cho JH; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.
  • Kim CD; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.
  • Kim YL; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.
  • Park SH; Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea.
Int J Mol Sci ; 22(18)2021 Sep 09.
Article en En | MEDLINE | ID: mdl-34575914
Recently, the role of kidney pericytes in kidney fibrosis has been investigated. This study aims to evaluate the effect of paricalcitol on hypoxia-induced and TGF-ß1-induced injury in kidney pericytes. The primary cultured pericytes were pretreated with paricalcitol (20 ng/mL) for 90 min before inducing injury, and then they were exposed to TGF-ß1 (5 ng/mL) or hypoxia (1% O2 and 5% CO2). TGF-ß1 increased α-SMA and other fibrosis markers but reduced PDGFRß expression in pericytes, whereas paricalcitol reversed the changes. Paricalcitol inhibited the TGF-ß1-induced cell migration of pericytes. Hypoxia increased TGF-ß1, α-SMA and other fibrosis markers but reduced PDGFRß expression in pericyte, whereas paricalcitol reversed them. Hypoxia activated the HIF-1α and downstream molecules including prolyl hydroxylase 3 and glucose transporter-1, whereas paricalcitol attenuated the activation of the HIF-1α-dependent molecules and TGF-ß1/Smad signaling pathways in hypoxic pericytes. The gene silencing of HIF-1α vanished the hypoxia-induced TGF-ß1, α-SMA upregulation, and PDGFRß downregulation. The effect of paricalcitol on the HIF-1α-dependent changes of fibrosis markers was not significant after the gene silencing of HIF-1α. In addition, hypoxia aggravated the oxidative stress in pericytes, whereas paricalcitol reversed the oxidative stress by increasing the antioxidant enzymes in an HIF-1α-independent manner. In conclusion, paricalcitol improved the phenotype changes of pericyte to myofibroblast in TGF-ß1-stimulated pericytes. In addition, paricalcitol improved the expression of fibrosis markers in hypoxia-exposed pericytes both in an HIF-1α-dependent and independent manner.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ergocalciferoles / Sustancias Protectoras / Pericitos / Factor de Crecimiento Transformador beta1 / Hipoxia Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ergocalciferoles / Sustancias Protectoras / Pericitos / Factor de Crecimiento Transformador beta1 / Hipoxia Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article Pais de publicación: Suiza