scholarly journals Role of Matricellular CCN Proteins in Skeletal Muscle: Focus on CCN2/CTGF and Its Regulation by Vasoactive Peptides

2021 ◽  
Vol 22 (10) ◽  
pp. 5234
Author(s):  
Daniela L. Rebolledo ◽  
María José Acuña ◽  
Enrique Brandan

The Cellular Communication Network (CCN) family of matricellular proteins comprises six proteins that share conserved structural features and play numerous biological roles. These proteins can interact with several receptors or soluble proteins, regulating cell signaling pathways in various tissues under physiological and pathological conditions. In the skeletal muscle of mammals, most of the six CCN family members are expressed during embryonic development or in adulthood. Their roles during the adult stage are related to the regulation of muscle mass and regeneration, maintaining vascularization, and the modulation of skeletal muscle fibrosis. This work reviews the CCNs proteins’ role in skeletal muscle physiology and disease, focusing on skeletal muscle fibrosis and its regulation by Connective Tissue Growth factor (CCN2/CTGF). Furthermore, we review evidence on the modulation of fibrosis and CCN2/CTGF by the renin-angiotensin system and the kallikrein-kinin system of vasoactive peptides.

2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Xiaoran Liu

Objective Long-term movement could induce micro-damage of skeletal muscle, increase collagen significantly, and appear skeletal muscle fibrosis. Vimentin is one of the most important proteins in evaluating the fibrosis after muscle injury. TGF-β1 could up-regulate Vimentin expression, promoting cell migration and accelerating fibrosis and injury repair. This study mainly explored the role of TGF-β1/Vim in skeletal muscle fibrosis affected by a bout of high-load exercise. And we tried to find whether the expression of vimentin could regulate the regeneration of muscle fiber and the remodeling of connective tissue. Methods SD rats were divided into 7groups: control group, immediately, 6-hour, 12-hour, 24-hour, 48-hour and 72-hour after group. Western Blot was used to detect TGF-β1, vimentin, RhoA, ROCK1 and CTGF(connective tissue growth factor) expressions. Electron microscopy was used to observe the changes of collagen in skeletal muscle. Results Vimentin protein exprsssion increased quickly at 6-hour after exerciese. At 48-hour, the vimentin expression reached the peak. And then the expression of vimentin gradually decreased. The expressions of TGF-β1, RhoA, ROCK1 and CTGF gradually increased after exercise. The peak of these expressions appeared at 12-hour respectively. Then these protein expressions declined slowly. Collagen in skeletal muscle became long and thick in 48-hour and 72-hour after exercise. Conclusions A bout of high-load exercise could induce skeletal muscle fibrosis. RhoA-ROCK1 maybe affect TGF-β1/Vim expressions as main regulators, and then the protein expression vimentin could regulate the regeneration of muscle fiber and the remodeling of connective tissue as an important evaluation factor.  


2010 ◽  
Vol 5 (5) ◽  
pp. 737-747 ◽  
Author(s):  
Sander Grefte ◽  
Anne Marie Kuijpers-Jagtman ◽  
Ruurd Torensma ◽  
Johannes W Von den Hoff

2018 ◽  
Vol 66 (23) ◽  
pp. 5802-5811 ◽  
Author(s):  
Haiou Pan ◽  
Yan Li ◽  
Haifeng Qian ◽  
Xiguang Qi ◽  
Gangcheng Wu ◽  
...  

2019 ◽  
Vol 82 ◽  
pp. 20-37 ◽  
Author(s):  
Daniela L. Rebolledo ◽  
David González ◽  
Jennifer Faundez-Contreras ◽  
Osvaldo Contreras ◽  
Carlos P. Vio ◽  
...  

2020 ◽  
Vol 5 (4) ◽  
pp. 2473011420S0046
Author(s):  
Ichiro Tonogai ◽  
Ichiro Tonogai

Category: Basic Sciences/Biologics Introduction/Purpose: Skeletal muscle fibrosis induced by the increase of collagen occurs after limb lengthening which is also called distraction osteogenesis. Although there are studies about influence of platelet rich plasma (PRP) on tissues healing process, its effectiveness is still controversial. The aim of this study was to examine whether PRP decreased the skeletal muscle fibrosis induced by limb lengthening. Methods: Tibial osteotomy was done to 8-week-old wild type mice. Tibia was lengthened at a rate of 0.42 mm/day during 2 weeks, launching 1 week after tibial osteotomy. Just after lengthening completed (3 weeks after tibial osteotomy), PRP was injected into the gastrocnemius muscle (PRP group). As a sham group, phosphate buffered saline (PBS) was injected into the gastrocnemius muscle (non-PRP group). The gastrocnemius (GC) muscles were taken and analyzed at 4, 6, 8 and 10 weeks after tibial osteotomy. Results: The fibrotic area of the GC muscles in the both groups increased at 4 weeks after tibial osteotomy in histological analysis (Figure). Then, it gradually decreased at 6, 8, and 10 weeks after tibial osteotomy. There were no significant differences between the both groups at 6, 8, and 10 weeks after tibial osteotomy. Hydroxyproline, which was a major constituent of collagen, increased in the non-PRP and PRP groups by limb lengthening as well. However, significant changes were not found between the both groups at all any points. Conclusion: At first, we anticipated that PRP should reduce the skeletal muscle fibrosis after limb lengthening significantly. But our results implied that PRP did not decrease the skeletal muscle fibrosis induced by limb lengthening.


2020 ◽  
Vol 21 (17) ◽  
pp. 6269
Author(s):  
Alee Choi ◽  
Sang Eon Park ◽  
Jang Bin Jeong ◽  
Suk-joo Choi ◽  
Soo-young Oh ◽  
...  

Extracellular matrix (ECM) components play an important role in maintaining skeletal muscle function, but excessive accumulation of ECM components interferes with skeletal muscle regeneration after injury, eventually inducing fibrosis. Increased oxidative stress level caused by dystrophin deficiency is a key factor in fibrosis in Duchenne muscular dystrophy (DMD) patients. Mesenchymal stem cells (MSCs) are considered a promising therapeutic agent for various diseases involving fibrosis. In particular, the paracrine factors secreted by MSCs play an important role in the therapeutic effects of MSCs. In this study, we investigated the effects of MSCs on skeletal muscle fibrosis. In 2–5-month-old mdx mice intravenously injected with 1 × 105 Wharton’s jelly (WJ)-derived MSCs (WJ-MSCs), fibrosis intensity and accumulation of calcium/necrotic fibers were significantly decreased. To elucidate the mechanism of this effect, we verified the effect of WJ-MSCs in a hydrogen peroxide-induced fibrosis myotubes model. In addition, we demonstrated that matrix metalloproteinase-1 (MMP-1), a paracrine factor, is critical for this anti-fibrotic effect of WJ-MSCs. These findings demonstrate that WJ-MSCs exert anti-fibrotic effects against skeletal muscle fibrosis, primarily via MMP-1, indicating a novel target for the treatment of muscle diseases, such as DMD.


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