Simultaneous inhibition of transforming growth factor-β (TGF-β) type I receptors Acvr1b and Tgfbr1 signalling has been associated with excessive skeletal muscle hypertrophy in vivo. However, it remains unclear whether the increased muscle mass in vivo is a direct result of inhibition of intracellular TGF-β signalling or whether this is an indirect effect of an altered extracellular anabolic environment. Here, we tested whether individual or simultaneous knockdown of TGF-β type I receptors in C2C12 myotubes was sufficient to induce muscle hypertrophy. The expression levels of TGF-β type I receptors Acvr1b and Tgfbr1 in myotubes were knocked down individually or in combination in the absence or presence of TGF-β1 and myostatin. Knocking down either Acvr1b or Tgfbr1 did not significantly change cell phenotype. Unexpectedly, simultaneous knockdown of both receptors reduced C2C12 myotube diameter, mRNA expression levels of Hgf, Ccn2 and Mymx with or without TGF-β1 and myostatin administration. In spite of decreased phosphorylation of Smad2/3, phosphorylation of P70S6K was reduced. In addition, the gene expression level of β1-syntrophin (Sntb1), which encodes a protein associated with the dystrophin-glycoprotein complex, was increased. Parallel experiments where Sntb1 gene expression was reduced showed an increase in myotube diameter and fusion of C2C12 myoblasts. Together, these results indicate that the knockdown of both TGF-β type I receptors reduced myotube diameter. This atrophic effect was attributed to reduced protein synthesis signalling and an increased expression of β1-syntrophin. These results have implications for our fundamental understanding of how TGF-β signalling regulates skeletal muscle size.
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http://dx.doi.org/10.1002/jcp.31418 | DOI Listing |
Chem Biodivers
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Gannan Medical University, Depatment of Medicinal Chemistry, Gannan Medical University, 341000, Ganzhou, CHINA.
Extracting natural active ingredients from plants is an effective way to develop and screen modern drugs. Psoralea corylifolia is a leguminous plant whose seeds have long been used as a Traditional Chinese Medicine to treat psoriasis, rheumatism, dermatitis, and other diseases. To date, several main compounds, including coumarins, flavonoids, monoterpene phenols, and benzofurans, have been identified from the seeds of Psoralea corylifolia.
View Article and Find Full Text PDFAsian Pac J Cancer Prev
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Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281 Yogyakarta, Indonesia.
Objective: Programmed cell death-1 (PD-1, encoded by PDCD1) regulatory network participates in glioblastoma multiforme development. However, such a network in trastuzumab-resistant human epidermal growth factor receptor 2-positive (HER2+) breast cancer remains to be determined. Accordingly, this study was aimed to explore the PD-1 regulatory network responsible for the resistance of breast cancer cells to trastuzumab through a bioinformatics approach.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Pharmacology, ISF College of Pharmacy, Ghal Kalan, GT Road, Moga, 142001, Punjab, India.
In examining the enduring consequences of diabetes, recent research has focused on the anticipated outcomes of the condition. Specifically, cognitive impairment has been linked to diabetes mellitus dating back to the discovery of insulin. This study delves into the neuroprotective effects of TZP, i.
View Article and Find Full Text PDFAnim Biotechnol
December 2025
Jilin Academy of Agricultural Sciences, Changchun, Jilin Province, China.
Copy number variations (CNV) are important genetic variations. The endogenous factors cobalamin receptor () and MIA SH3 domain ER-derived factor 3 () are associated with bone/muscle development and intramuscular fat deposition. There have been no reports on the effects of and CNVs on growth traits of Chinese cattle.
View Article and Find Full Text PDFJ Crohns Colitis
January 2025
Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Background And Aims: Protein tyrosine phosphatase non-receptor type 23 (PTPN23) regulates the internalization of growth factor receptors such as the epithelial growth factor receptor (EGFR). Given the crucial function of such receptors in intestinal epithelial cells (IECs), we assessed the involvement of PTPN23 in intestinal homeostasis and epithelial proliferation.
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