Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023:1408:219-234.
doi: 10.1007/978-3-031-26163-3_12.

Differential Fibrotic Response of Muscle Fibroblasts, Myoblasts, and Myotubes to Cholic and Deoxycholic Acids

Luis Maldonado  1   2   3 , Josué Orozco-Aguilar  1   2   3   4   5 , Mayalen Valero-Breton  1   2   3 , Franco Tacchi  1   2   3 , Eduardo Cifuentes-Silva  1   2   3 , Claudio Cabello-Verrugio  6   7   8
Affiliations

Differential Fibrotic Response of Muscle Fibroblasts, Myoblasts, and Myotubes to Cholic and Deoxycholic Acids

Luis Maldonado et al. Adv Exp Med Biol. 2023.

Abstract

Fibrosis is a condition characterized by an increase in the components of the extracellular matrix (ECM). In skeletal muscle, the cells that participate in the synthesis of ECM are fibroblasts, myoblasts, and myotubes. These cells respond to soluble factors that increase ECM. Fibrosis is a phenomenon that develops in conditions of chronic inflammation, extensive lesions, or chronic diseases. A pathological condition with muscle weakness and increased bile acids (BA) in the blood is cholestatic chronic liver diseases (CCLD). Skeletal muscle expresses the membrane receptor for BA called TGR5. To date, muscle fibrosis in CCLD has not been evaluated. This study aims to assess whether BA can induce a fibrotic condition in muscle fibroblasts, myoblasts, and myotubes. The cells were incubated with deoxycholic (DCA) and cholic (CA) acids, and fibronectin protein levels were evaluated by Western blot. In muscle fibroblasts, both DCA and CA induced an increase in fibronectin protein levels. The same response was found in fibroblasts when activating TGR5 with the specific receptor agonist (INT-777). Interestingly, DCA reduced fibronectin protein levels in both myoblasts and myotubes, while CA did not show changes in fibronectin protein levels in myoblasts and myotubes. These results suggest that DCA and CA can induce a fibrotic phenotype in muscle-derived fibroblasts. On the other hand, DCA decreased the fibronectin in myoblasts and myotubes, whereas CA did not show any effect in these cell populations. Our results show that BA has different effects depending on the cell population to be analyzed.

Keywords: Bile acids; Fibronectin; Fibrosis; Liver diseases; Skeletal muscle cells; TGR5 receptor.

PubMed Disclaimer

Similar articles

See all similar articles

References

    1. Wynn TA (2008) Cellular and molecular mechanisms of fibrosis. J Pathol 214(2):199–210. https://doi.org/10.1002/path.2277 - DOI - PubMed - PMC
    1. Brandan E, Gutierrez J (2013) Role of proteoglycans in the regulation of the skeletal muscle fibrotic response. FEBS J 280(17):4109–4117. https://doi.org/10.1111/febs.12278 - DOI - PubMed
    1. Mann CJ, Perdiguero E, Kharraz Y, Aguilar S, Pessina P, Serrano AL et al (2011) Aberrant repair and fibrosis development in skeletal muscle. Skelet Muscle 1(1):21. https://doi.org/10.1186/2044-5040-1-21 - DOI - PubMed - PMC
    1. Vial C, Zuniga LM, Cabello-Verrugio C, Canon P, Fadic R, Brandan E (2008) Skeletal muscle cells express the profibrotic cytokine connective tissue growth factor (CTGF/CCN2), which induces their dedifferentiation. J Cell Physiol 215(2):410–421. https://doi.org/10.1002/jcp.21324 - DOI - PubMed
    1. Beach RL, Rao JS, Festoff BW (1985) Extracellular-matrix synthesis by skeletal muscle in culture. Major secreted collagenous proteins of clonal myoblasts. Biochem J 225(3):619–627. https://doi.org/10.1042/bj2250619

LinkOut - more resources

-