Association of myostatin deficiency with collagen related disease-umbilical hernia and tippy toe standing in pigs

• Published in: Transgenic research 2021-10, Vol.30 (5), p.663-674
• Main Authors: Paek, Hyo-Jin, Luo, Zhao-Bo, Choe, Hak-Myong, Quan, Biao-Hu, Gao, Kai, Han, Sheng-Zhong, Li, Zhou-Yan, Kang, Jin-Dan, Yin, Xi-Jun
• Format: Article
• Language: English
• Subjects: Activin; Animal Genetics and Genomics; Animals; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Body weight; Collagen; Collagen (type I); Collagen - genetics; Cyclin-dependent kinase; Cyclin-dependent kinase inhibitor p21; Cyclin-dependent kinases; Enzyme inhibitors; Fibroblasts; Gene expression; Genetic Engineering; Hernia; Hernia, Umbilical - genetics; Hernias; Kinases; Life Sciences; Male; Molecular Medicine; Muscle, Skeletal; Myostatin; Myostatin - genetics; Nuclear transfer; Nuclear Transfer Techniques; Original Paper; Phosphorylation; Plant Genetics and Genomics; Smad2 protein; Somatic cell nuclear transfer; Swine; Therapeutic targets; Toes; Transgenics
• ISSN: 0962-8819; 1573-9368
• DOI: 10.1007/s11248-021-00275-6

Herein, we investigate the high incidence of umbilical hernia and tippy-toe standing and their underlying changes in gene expression and proliferation in myostatin knockout ( MSTN −/− ) pigs. Thirty-six male MSTN −/− pigs were generated by somatic cell nuclear transfer (SCNT). These pigs presented a considerably high incidence of tippy-toe standing and umbilical hernia (69.4% and 61.1%, respectively). The tendon to body weight ratio was significantly lower than wild-type pigs (0.202 ± 0.017 vs 0.250 ± 0.004, respectively). The crimp length of the MSTN −/− tendon was significantly longer than that of wild-type pigs. The expression of MSTN and the activin type IIB ( ACVR2B ) was detected in the tendon and linea alba of MSTN −/− pigs. MSTN treatment significantly increased the phosphorylation of Smad2/3 in both tendon and linea alba fibroblasts. Type I collagen ( Col1A ) and Scleraxis ( Scx ) expression levels in the tendon and linea alba of MSTN −/− pigs were significantly lower than those in wild-type in vivo, whereas and cyclin-dependent kinase inhibitor 1 ( p21 ) expression levels were higher. Treatment of tendon and linea alba fibroblasts with recombinant MSTN increased Col1A and Scx and decreased p21 expression in vivo. Moreover, there was a significant increase in fibroblast proliferation after treatment. The results indicated that MSTN regulates collagen expression and proliferation in tendon and linea alba fibroblasts; thus, MSTN deficiency causes collagen-related pathological features in MSTN −/− pigs. Hence, MSTN could be used as a therapeutic target for treating UH and tendon abnormalities.