Dataset Information

Regulatory role of vitamin D3 on myogenesis and fibrogenesis under Vdr gene silencing and TGF-β1 stimulation in skeletal muscle cells

ABSTRACT: Vitamin D deficiency is associated with a decline in muscle function and an increasing risk of muscle injury in athletes and the elderly. Nevertheless, how vitamin D3 and vitamin D receptor (VDR) regulate skeletal muscle cells under pro-fibrotic factor stimulation that could be pronounced during repetitive muscle damage have not been elucidated. Therefore, this study aimed to investigate the regulatory role of cholecalciferol (D3), calcidiol (25D3), calcitriol (1,25D3), and the effect of Vdr gene suppression under TGF-β1 stimulation in C2C12 mouse skeletal muscle cells. All forms of vitamin D3 exerted anti-fibrotic effects under TGF-β1 stimulation by suppression of COL1A1; however, D3 preserves this effect without a negative impact on myogenesis. Moreover, LC-MS/MS-based proteomics analysis revealed that myoblast fusion protein and mitochondrial regulation were altered following Vdr knockdown. These changes were associated with exacerbation of α-SMA expression in TGF-β1-treated cells and suggested VDR modulates fibrogenesis in skeletal muscle cells regardless of ligand binding. Under TGF-β1 stimulation, anti-fibrotic effects of 1,25D3 but not D3 were diminished after Vdr knockdown, supporting D3 action is not dependent on VDR activation. Collectively, understanding anti-fibrotic effects of vitamin D3 is beneficial for providing a strategy of vitamin D supplementation to counteract fibrosis development after muscle injury.

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ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Ratchakrit Srikuea

LAB HEAD: Ratchakrit Srikuea

PROVIDER: PXD062669 | Pride | 2025-12-01

REPOSITORIES: Pride

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Regulatory role of vitamin D3 on myogenesis and fibrogenesis under Vdr gene silencing and TGF-β1 stimulation in skeletal muscle cells.

Watcharanapapan Wasina W Hirunsai Muthita M Srikuea Ratchakrit R

Scientific reports 20251124 1

Vitamin D deficiency is associated with a decline in muscle function and an increasing risk of muscle injury in athletes and the elderly. Nevertheless, how vitamin D3 and vitamin D receptor (VDR) regulate skeletal muscle cells under profibrotic factor stimulation that could be pronounced during repetitive muscle damage have not been elucidated. Therefore, this study aimed to investigate the regulatory role of cholecalciferol (D3), calcidiol (25D3), calcitriol (1, ...[more]

PMID: 41286086

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Project description:Venkatraman2012 - Interplay between PLS and TSP1 in TGF-β1 activation The interplay between PLS (Plasmin) and TSP1 (Thrombospondin-1) in TGF-β1 (Transforming growth factor-β1)is shown using mathematical modelling and in vitro experimentents. This model is described in the article: Plasmin triggers a switch-like decrease in thrombospondin-dependent activation of TGF-β1. Venkatraman L, Chia SM, Narmada BC, White JK, Bhowmick SS, Forbes Dewey C Jr, So PT, Tucker-Kellogg L, Yu H. Biophys J. 2012 Sep 5;103(5):1060-8. Abstract: Transforming growth factor-β1 (TGF-β1) is a potent regulator of extracellular matrix production, wound healing, differentiation, and immune response, and is implicated in the progression of fibrotic diseases and cancer. Extracellular activation of TGF-β1 from its latent form provides spatiotemporal control over TGF-β1 signaling, but the current understanding of TGF-β1 activation does not emphasize cross talk between activators. Plasmin (PLS) and thrombospondin-1 (TSP1) have been studied individually as activators of TGF-β1, and in this work we used a systems-level approach with mathematical modeling and in vitro experiments to study the interplay between PLS and TSP1 in TGF-β1 activation. Simulations and steady-state analysis predicted a switch-like bistable transition between two levels of active TGF-β1, with an inverse correlation between PLS and TSP1. In particular, the model predicted that increasing PLS breaks a TSP1-TGF-β1 positive feedback loop and causes an unexpected net decrease in TGF-β1 activation. To test these predictions in vitro, we treated rat hepatocytes and hepatic stellate cells with PLS, which caused proteolytic cleavage of TSP1 and decreased activation of TGF-β1. The TGF-β1 activation levels showed a cooperative dose response, and a test of hysteresis in the cocultured cells validated that TGF-β1 activation is bistable. We conclude that switch-like behavior arises from natural competition between two distinct modes of TGF-β1 activation: a TSP1-mediated mode of high activation and a PLS-mediated mode of low activation. This switch suggests an explanation for the unexpected effects of the plasminogen activation system on TGF-β1 in fibrotic diseases in vivo, as well as novel prognostic and therapeutic approaches for diseases with TGF-β dysregulation. This model is hosted on BioModels Database and identified by: MODEL1303130000 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

			Action	DRS
	Control_siRNA_1.raw	Raw
	Control_siRNA_2.raw	Raw
	Vdr_siRNA_1.raw	Raw
	Vdr_siRNA_2.raw	Raw
	Vdr_siRNA_vs_Control_siRNA.mzTab	Mztab

Dataset Information

Regulatory role of vitamin D3 on myogenesis and fibrogenesis under Vdr gene silencing and TGF-β1 stimulation in skeletal muscle cells

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Regulatory role of vitamin D<sub>3</sub> on myogenesis and fibrogenesis under Vdr gene silencing and TGF-β1 stimulation in skeletal muscle cells.

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Dataset Information

Regulatory role of vitamin D3 on myogenesis and fibrogenesis under Vdr gene silencing and TGF-β1 stimulation in skeletal muscle cells

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Regulatory role of vitamin D&lt;sub&gt;3&lt;/sub&gt; on myogenesis and fibrogenesis under Vdr gene silencing and TGF-β1 stimulation in skeletal muscle cells.

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OmicsDI is part of the ELIXIR infrastructure

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Regulatory role of vitamin D<sub>3</sub> on myogenesis and fibrogenesis under Vdr gene silencing and TGF-β1 stimulation in skeletal muscle cells.