Expression of TGF-<i>β</i>1 and CTGF Is Associated with Fibrosis of Denervated Sternocleidomastoid Muscles in Mice

Abstract

Injury to the recurrent laryngeal nerve often leads to permanent vocal cord paralysis, which has a significant negative impact on the quality of life. Long-term denervation can induce laryngeal muscle fibrosis，which obstructs the muscle recovery after laryngeal reinnervation. However, the mechanisms of fibrosis remain unclear. In this study, we aimed to analyze the changes in the expression of fibrosis-related factors, including transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) in denervated skeletal muscles using a mouse model of accessory nerve transection. Because of the small size, we used sternocleidomastoid muscles instead of laryngeal muscles for denervation experiments. Masson's trichrome staining showed that the grade of atrophy and fibrosis of muscles became more severe with time, but showed a plateau at 4 weeks after denervation, followed by a slow decrease. Quantitative assessment and immunohistochemistry showed that TGF-β1 expression peaked at 1 week after denervation (p < 0.05) and was maintained at its high level until 4 weeks. CTGFand α-SMA-positive muscle cells were detected at 1 week after denervation, peaked at 2 weeks (p < 0.05), and remained at high levels with a subsequent slight decrease for 3-4 weeks. These results suggest that TGF-β1 and CTGF may be involved in the process of denervated skeletal muscle fibrosis. They may induce the differentiation of myoblasts into myofibroblasts, as characterized by the activation of α-SMA. These findings may provide insights on key pathological processes in denervated skeletal muscle fibrosis and develop novel therapeutic strategies.

MicroRNA-27a Suppresses Detrusor Fibrosis in Streptozotocin-Induced Diabetic Rats by Targeting PRKAA2 Through the TGF-β1/Smad3 Signaling Pathway

“…Consistent with the present study, dilation of the endoplasmic reticulum and swelling of mitochondria in cytoplasts were observed in diabetes, and the filaments were severely decreased [38]. TGF-β1 and CTGF have been associated with enervated skeletal muscle fibrosis and promote myoblasts differentiation into myofibroblasts [39]. Moreover, miR-27a is correlated with expressional changes of TGF-β1, CTGF, FN and COL-I in renal tubulointerstitial fibrosis [21].…”

“…Knockdown of PRKAA2 suppresses epithelial-mesenchymal transition (EMT) and secretion of chemokines in renal tubular epithelia by interacting with CK2β and TGFβ1/Smad to attenuate renal injury [44]. Additionally, TGF-β1 and CTGF might be correlated with denervated skeletal muscle fibrosis and promote myoblasts differentiation into myofibroblasts [39]. Moreover, the TGF-β1/Smad3 signaling pathway is a significant part of the development of renal interstitial fibrosis, and expression of Smad3 is positively associated with the RIF index and protein expression of TGF-β1, Col-IV, and FN [45].…”

Antiapoptosis and Antifibrosis Effects of Qishen Granules on Heart Failure Rats via Hippo Pathway

“…CTGF, downstream target of YAP/TAZ, is another factor that can act as a bridge between Hippo and TGF-β pathway to induce fibrosis [43,44]. Numerous studies show that therapeutic strategies aimed at inhibition of above profibrotic proteins are beneficial for treating HF [45][46][47]. e protein levels of YAP, TAZ, TGF-β1, SMAD3, and CTGF were all downregulated with the administration of QSG.…”

HO-1/EBP interaction alleviates cholesterol-induced hypoxia through the activation of the AKT and Nrf2/mTOR pathways and inhibition of carbohydrate metabolism in cardiomyocytes

“…The ICC was performed as in a previous study (26). Briefly, the cells and 5 frozen slices from four groups were fixed in pre-cooling methanol for 10 min and then permeabilized with 0.5% Triton X-100 for 20 min at 37°C.…”