Paricalcitol Improves Hypoxia-Induced and TGF-β1-Induced Injury in Kidney Pericytes |
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Authors: | Jeong-Hoon Lim Ju-Min Yook Se-Hyun Oh Soo-Jee Jeon Hee Won Noh Hee-Yeon Jung Ji-Young Choi Jang-Hee Cho Chan-Duck Kim Yong-Lim Kim Sun-Hee Park |
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Affiliation: | Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea; (J.-H.L.); (J.-M.Y.); (S.-H.O.); (S.-J.J.); (H.W.N.); (H.-Y.J.); (J.-Y.C.); (J.-H.C.); (C.-D.K.); (Y.-L.K.) |
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Abstract: | 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-β1-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-β1 (5 ng/mL) or hypoxia (1% O2 and 5% CO2). TGF-β1 increased α-SMA and other fibrosis markers but reduced PDGFRβ expression in pericytes, whereas paricalcitol reversed the changes. Paricalcitol inhibited the TGF-β1-induced cell migration of pericytes. Hypoxia increased TGF-β1, α-SMA and other fibrosis markers but reduced PDGFRβ 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-β1/Smad signaling pathways in hypoxic pericytes. The gene silencing of HIF-1α vanished the hypoxia-induced TGF-β1, α-SMA upregulation, and PDGFRβ 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-β1-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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Keywords: | hypoxia paricalcitol pericyte pericyte– to– myofibroblast transition TGF-β 1 vitamin D agonist |
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