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KAP1 modulates osteogenic differentiation via the ERK/Runx2 cascade in vascular smooth muscle cells

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A Correction to this article was published on 04 July 2023

A Correction to this article was published on 26 May 2023

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Abstract

Background

Osteoblast phenotypic transition in vascular smooth muscle cells (VSMCs) has been unveiled as a common cause of vascular calcification (VC). Krüppel-Associated Box (KRAB)-Associated Protein 1(KAP1) is a transcriptional corepressor that modulates various intracellular pathological processes from gene expression to DNA repair to signal transduction. However, the function and mechanism of KAP1 on the osteoblastic differentiation of VSMCs have not been evaluated yet.

Methods and results

We demonstrate that the expression of KAP1 in VSMCs is significantly enhanced in vivo and in vitro calcification models. Downregulating the expression of KAP1 suppresses the osteoblast phenotypic transition of VSMCs, which is indicated by a decrease in the expression of osteoblast marker collagenase type I (COL I) and an increase in the expression of VSMC marker α-smooth muscle actin (α-SMA). Conversely, exogenous overexpression of KAP1 could promote osteoblast phenotypic transition of VSMCs. Moreover, KAP1 upregulated the expression of RUNX family transcription factor 2 (Runx2), an inducer of osteoblast that positively regulates many osteoblast-related genes, such as COL I. Evaluation of the potential mechanism demonstrated that KAP1 promoted osteoblast phenotypic transition of VSMCs by activating the extracellular regulated protein kinases (ERK) signaling pathway, which could activate Runx2. In support of this finding, KAP1-induced cell osteoblast phenotypic transition is abolished by treatment with PD0325901, a specific ERK inhibitor.

Conclusions

The present study suggested that KAP1 participated in the osteoblast differentiation of VSMCs via the ERK/Runx2 cascade and served as a potential diagnostics and therapeutics target for vascular calcification.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Funding

This work was supported by The Project of Hebei Clinical Medicine Outstanding Personnel Training (2019139), Hebei Province Medical Technology Tracking Project (G2018050), Hebei Province Key Research and Development Project (20377704D), and Hebei Province Innovation Capacity Improvement Project (20577701D).

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Authors and Affiliations

  1. Department of Nephrology, The Fourth Hospital of Hebei Medical University, Hebei Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Shijiazhuang, P.R. China

    Weiwei Bai, Meijuan Cheng, Jingjing Jin, Dongxue Zhang, Lanmei Li, Yaling Bai & Jinsheng Xu

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  1. Weiwei Bai
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Contributions

YLB and JSX conceived the study. WWB and DXZ performed the follow-up experiments and wrote the manuscript. LML performed data collections and calculations. MJC and JJJ oversaw language editing. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jinsheng Xu.

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The authors declare that there are no conflict of interest associated with the manuscript.

Ethical approval

The experimental protocols were reviewed and approved by the Animal Care and Use Institutional Committee of The Fourth Affiliated Hospital of Hebei Medical University (No. 2020ky189).

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The original online version of this article was revised: The affiliation is corrected as “Department of Nephrology, The Fourth Hospital of Hebei Medical University, Hebei Clinical Research Center for Chronic Kidney Disease, Hebei Key Laboratory of Vascular Calcification in Kidney Disease, Shijiazhuang P.R. China”

The original online version of this article was revised: The figures 1G, 2E and 3C have been corrected.

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Bai, W., Cheng, M., Jin, J. et al. KAP1 modulates osteogenic differentiation via the ERK/Runx2 cascade in vascular smooth muscle cells. Mol Biol Rep 50, 3217–3228 (2023). https://doi.org/10.1007/s11033-022-08225-z

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  • DOI: https://doi.org/10.1007/s11033-022-08225-z

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