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

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.

• 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
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 18 (Sep 09 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34575914 (Publication Type: Journal Article)

Chemical References

• Ergocalciferols
• Hypoxia-Inducible Factor 1, alpha Subunit
• Protective Agents
• Smad2 Protein
• Transforming Growth Factor beta1
• paricalcitol

Topics

• Animals
• Cells, Cultured
• Ergocalciferols (pharmacology)
• Fibrosis
• Hypoxia (genetics, metabolism)
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Kidney (drug effects, metabolism, pathology)
• Mice
• Myofibroblasts (drug effects, metabolism)
• Oxidative Stress
• Pericytes (drug effects, metabolism, pathology)
• Phosphorylation
• Protective Agents (pharmacology)
• Signal Transduction (drug effects)
• Smad2 Protein (metabolism)
• Transforming Growth Factor beta1 (metabolism)