TGF-β Regulates Collagen Type I Expression in Myoblasts and Myotubes Via Transient and Expression

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2020 Feb 12

PMID 32041253

Citations 31

Authors

Michele M G Hillege

Ricardo A Galli Caro

Carla Offringa

Gerard M J de Wit

Richard T Jaspers

Willem M H Hoogaars

Affiliations

Soon will be listed here.

Abstract

Transforming Growth Factor β (TGF-β) is involved in fibrosis as well as the regulation of muscle mass, and contributes to the progressive pathology of muscle wasting disorders. However, little is known regarding the time-dependent signalling of TGF-β in myoblasts and myotubes, as well as how TGF-β affects collagen type I expression and the phenotypes of these cells. Here, we assessed effects of TGF-β on gene expression in C2C12 myoblasts and myotubes after 1, 3, 9, 24 and 48 h treatment. In myoblasts, various myogenic genes were repressed after 9, 24 and 48 h, while in myotubes only a reduction in expression was observed. In both myoblasts and myotubes, TGF-β acutely induced the expression of a subset of genes involved in fibrosis, such as and which was subsequently followed by increased expression of . Knockdown of and resulted in a lower expression level. Furthermore, the effects of TGF-β on myogenic and fibrotic gene expression were more pronounced than those of myostatin, and knockdown of TGF-β type I receptor , but not receptor resulted in a reduction in and expression. These results indicate that, during muscle regeneration, TGF-β induces fibrosis via by stimulating the autocrine signalling of and

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References

Gillies A, Lieber R . Structure and function of the skeletal muscle extracellular matrix. Muscle Nerve. 2011; 44(3):318-31. PMC: 3177172. DOI: 10.1002/mus.22094. View

Avin K, Chen N, Organ J, Zarse C, ONeill K, Conway R . Skeletal Muscle Regeneration and Oxidative Stress Are Altered in Chronic Kidney Disease. PLoS One. 2016; 11(8):e0159411. PMC: 4972446. DOI: 10.1371/journal.pone.0159411. View

Ramachandran A, Vizan P, Das D, Chakravarty P, Vogt J, Rogers K . TGF-β uses a novel mode of receptor activation to phosphorylate SMAD1/5 and induce epithelial-to-mesenchymal transition. Elife. 2018; 7. PMC: 5832415. DOI: 10.7554/eLife.31756. View

Carlson M, Hsu M, Conboy I . Imbalance between pSmad3 and Notch induces CDK inhibitors in old muscle stem cells. Nature. 2008; 454(7203):528-32. PMC: 7761661. DOI: 10.1038/nature07034. View

Li Y, Foster W, Deasy B, Chan Y, Prisk V, Tang Y . Transforming growth factor-beta1 induces the differentiation of myogenic cells into fibrotic cells in injured skeletal muscle: a key event in muscle fibrogenesis. Am J Pathol. 2004; 164(3):1007-19. PMC: 1614716. DOI: 10.1016/s0002-9440(10)63188-4. View

Lima J, Simoes E, de Castro G, Morais M, de Matos-Neto E, Alves M . Tumour-derived transforming growth factor-β signalling contributes to fibrosis in patients with cancer cachexia. J Cachexia Sarcopenia Muscle. 2019; 10(5):1045-1059. PMC: 6818454. DOI: 10.1002/jcsm.12441. View

Shur I, Lokiec F, Bleiberg I, Benayahu D . Differential gene expression of cultured human osteoblasts. J Cell Biochem. 2001; 83(4):547-53. DOI: 10.1002/jcb.1249. View

Mendias C, Gumucio J, Davis M, Bromley C, Davis C, Brooks S . Transforming growth factor-beta induces skeletal muscle atrophy and fibrosis through the induction of atrogin-1 and scleraxis. Muscle Nerve. 2011; 45(1):55-9. PMC: 3245632. DOI: 10.1002/mus.22232. View

Yablonka-Reuveni Z, Rivera A . Proliferative Dynamics and the Role of FGF2 During Myogenesis of Rat Satellite Cells on Isolated Fibers. Basic Appl Myol. 2015; 7(3-amp4):189-202. PMC: 4457462. View

10.

Lin C, Yu M, Tung W, Chen T, Yu C, Weng C . Connective tissue growth factor induces collagen I expression in human lung fibroblasts through the Rac1/MLK3/JNK/AP-1 pathway. Biochim Biophys Acta. 2013; 1833(12):2823-2833. DOI: 10.1016/j.bbamcr.2013.07.016. View

11.

Chen J, Walton K, Hagg A, Colgan T, Johnson K, Qian H . Specific targeting of TGF-β family ligands demonstrates distinct roles in the regulation of muscle mass in health and disease. Proc Natl Acad Sci U S A. 2017; 114(26):E5266-E5275. PMC: 5495232. DOI: 10.1073/pnas.1620013114. View

12.

Thomas K, Engler A, Meyer G . Extracellular matrix regulation in the muscle satellite cell niche. Connect Tissue Res. 2014; 56(1):1-8. PMC: 4464813. DOI: 10.3109/03008207.2014.947369. View

13.

Kadoguchi T, Shimada K, Koide H, Miyazaki T, Shiozawa T, Takahashi S . Possible Role of NADPH Oxidase 4 in Angiotensin II-Induced Muscle Wasting in Mice. Front Physiol. 2018; 9:340. PMC: 5895660. DOI: 10.3389/fphys.2018.00340. View

14.

Bo Li Z, Kollias H, Wagner K . Myostatin directly regulates skeletal muscle fibrosis. J Biol Chem. 2008; 283(28):19371-8. PMC: 2443655. DOI: 10.1074/jbc.M802585200. View

15.

Ryall J, Schertzer J, Lynch G . Cellular and molecular mechanisms underlying age-related skeletal muscle wasting and weakness. Biogerontology. 2008; 9(4):213-28. DOI: 10.1007/s10522-008-9131-0. View

16.

Huijing P, Jaspers R . Adaptation of muscle size and myofascial force transmission: a review and some new experimental results. Scand J Med Sci Sports. 2005; 15(6):349-80. DOI: 10.1111/j.1600-0838.2005.00457.x. View

17.

Liu D, Black B, Derynck R . TGF-beta inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3. Genes Dev. 2001; 15(22):2950-66. PMC: 312830. DOI: 10.1101/gad.925901. View

18.

Kemaladewi D, de Gorter D, Aartsma-Rus A, van Ommen G, Ten Dijke P, t Hoen P . Cell-type specific regulation of myostatin signaling. FASEB J. 2011; 26(4):1462-72. DOI: 10.1096/fj.11-191189. View

19.

Shi Y, Massague J . Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 2003; 113(6):685-700. DOI: 10.1016/s0092-8674(03)00432-x. View

20.

Massague J, Cheifetz S, Endo T, Nadal-Ginard B . Type beta transforming growth factor is an inhibitor of myogenic differentiation. Proc Natl Acad Sci U S A. 1986; 83(21):8206-10. PMC: 386896. DOI: 10.1073/pnas.83.21.8206. View