Paricalcitol Improves Hypoxia-Induced and TGF-β1-Induced Injury in Kidney Pericytes

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-beta 1-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-beta 1 (5 ng/mL) or hypoxia (1% O-2 and 5% CO2). TGF-beta 1 increased alpha-SMA and other fibrosis markers but reduced PDGFR beta expression in pericytes, whereas paricalcitol reversed the changes. Paricalcitol inhibited the TGF-beta 1-induced cell migration of pericytes. Hypoxia increased TGF-beta 1, alpha-SMA and other fibrosis markers but reduced PDGFR beta expression in pericyte, whereas paricalcitol reversed them. Hypoxia activated the HIF-1 alpha and downstream molecules including prolyl hydroxylase 3 and glucose transporter-1, whereas paricalcitol attenuated the activation of the HIF-1 alpha-dependent molecules and TGF-beta 1/Smad signaling pathways in hypoxic pericytes. The gene silencing of HIF-1 alpha vanished the hypoxia-induced TGF-beta 1, alpha-SMA upregulation, and PDGFR beta downregulation. The effect of paricalcitol on the HIF-1 alpha-dependent changes of fibrosis markers was not significant after the gene silencing of HIF-1 alpha. In addition, hypoxia aggravated the oxidative stress in pericytes, whereas paricalcitol reversed the oxidative stress by increasing the antioxidant enzymes in an HIF-1 alpha-independent manner. In conclusion, paricalcitol improved the phenotype changes of pericyte to myofibroblast in TGF-beta 1-stimulated pericytes. In addition, paricalcitol improved the expression of fibrosis markers in hypoxia-exposed pericytes both in an HIF-1 alpha-dependent and independent manner.