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Long non-coding RNA H19 promotes osteogenic differentiation of renal interstitial fibroblasts through Wnt-β-catenin pathway

Authors
  • Zhu, Zewu1
  • Cui, Yu1
  • Huang, Fang1
  • Zeng, Huimin1
  • Xia, Weiping1
  • Zeng, Feng1
  • He, Cheng1
  • Chen, Jinbo1
  • Chen, Zhiyong1
  • Chen, Hequn1
  • Li, Yang1
  • 1 Central South University, Changsha, Hunan, 410008, China , Changsha (China)
Type
Published Article
Journal
Molecular and Cellular Biochemistry
Publisher
Springer-Verlag
Publication Date
May 21, 2020
Volume
470
Issue
1-2
Pages
145–155
Identifiers
DOI: 10.1007/s11010-020-03753-3
Source
Springer Nature
Keywords
License
Yellow

Abstract

Randall’s plaque (RP) serves as a nidus on which idiopathic calcium oxalate stones form. Renal interstitial mineralization may be the cause underlying RP, and recent studies demonstrated the similarities between the interstitial mineralization and ectopic calcification. The present study aimed to investigate whether human renal interstitial fibroblasts (hRIFs) could form calcification under osteogenic conditions, and whether long non-coding RNA H19 participated in regulating osteogenic differentiation of hRIFs through Wnt-β-catenin pathway. HRIFs were isolated and induced for osteogenic differentiation under osteogenic conditions. Runx2, OCN, alkaline phosphatase (ALP) activity, and the mineralized nodule formation were used to assess the osteogenic phenotype. Molecule expressions were determined by qRT-PCR, immunofluorescence staining, and western blot. The mineralized nodules were assessed by Alizarin red staining. Compared to the normal renal papillary tissue, Runx2, OCN, and H19 were significantly upregulated in RP. After hRIFs were induced with osteogenic medium, osteogenic markers (Runx2, OCN and ALP), β‐catenin and H19 were significantly upregulated, and the mineralized nodules are formed. Additionally, overexpression of H19 promoted the osteogenic phenotype of hRIFs and increased the expression of β‐catenin, whereas knock-down of H19 or XAV939 (inhibitor of Wnt-β‐catenin signaling pathway) significantly repressed the osteogenic phenotype of hRIFs and decreased the β‐catenin. Moreover, XAV939 was shown to abolish the osteogenic differentiation of hRIFs promoted by H19. The study demonstrated that ectopic calcification partly participated in the formation of RP, and H19 promoted osteogenic differentiation of hRIFs by activating Wnt-β-catenin pathway, which shed new light on the molecular mechanism of the RP formation.

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