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

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A Correction to this article was published on 07 July 2020

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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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  • 07 July 2020

    In the original article, Fig.��2c was published incorrectly. The correct version of Fig.��2c is provided in this correction.

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Acknowledgements

We are grateful for the funding provided by the Nature Science Foundation of Hunan province, China 2017JJ2395 (to Yang Li).

Funding

This study was funded by the Nature Science Foundation of Hunan province, China (2017JJ2395).

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  1. Zewu Zhu and Yu Cui have contributed equally to the article.

Authors and Affiliations

  1. Department of Urology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Zewu Zhu, Yu Cui, Fang Huang, Huimin Zeng, Weiping Xia, Feng Zeng, Cheng He, Jinbo Chen, Zhiyong Chen, Hequn Chen & Yang Li

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Contributions

Conceptualization: ZZ, YC; Methodology: FH, YC, FZ; Formal analysis and investigation: ZZ, HZ, WX; Writing-original draft preparation: ZZ; Writing-review and editing: YC, JC; Funding acquisition: YL; Resources: ZC, CH; Supervision: HC, YL.

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Correspondence to Yang Li.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Xiangya Hospital of Central South University (Date: July 23, 2017 /No.201705768).

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Zhu, Z., Cui, Y., Huang, F. et al. Long non-coding RNA H19 promotes osteogenic differentiation of renal interstitial fibroblasts through Wnt-β-catenin pathway. Mol Cell Biochem 470, 145–155 (2020). https://doi.org/10.1007/s11010-020-03753-3

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