scholarly journals Cellular Mechanisms of Tissue Fibrosis. 4. Structural and functional consequences of skeletal muscle fibrosis

2013 ◽  
Vol 305 (3) ◽  
pp. C241-C252 ◽  
Author(s):  
Richard L. Lieber ◽  
Samuel R. Ward
Keyword(s):  
Skeletal Muscle ◽  
Structural Model ◽  
Transforming Growth Factor ◽  
Clinical Problem ◽  
Transforming Growth Factor Β ◽  
Common Mechanism ◽  
Cellular Mechanisms ◽  
Muscle Fibrosis ◽  
Activated Fibroblasts ◽  
Skeletal Muscle Fibrosis

Skeletal muscle fibrosis can be a devastating clinical problem that arises from many causes, including primary skeletal muscle tissue diseases, as seen in the muscular dystrophies, or it can be secondary to events that include trauma to muscle or brain injury. The cellular source of activated fibroblasts (myofibroblasts) may include resident fibroblasts, adult muscle stem cells, or inflammatory or perivascular cells, depending on the model studied. Even though it is likely that there is no single source for all myofibroblasts, a common mechanism for the production of fibrosis is via the transforming growth factor-β/phosphorylated Smad3 pathway. This pathway and its downstream targets thus provide loci for antifibrotic therapies, as do methods for blocking the transdifferentiation of progenitors into activated fibroblasts. A structural model for the extracellular collagen network of skeletal muscle is needed so that measurements of collagen content, morphology, and gene expression can be related to mechanical properties. Approaches used to study fibrosis in tissues, such as lung, kidney, and liver, need to be applied to studies of skeletal muscle to identify ways to prevent or even cure the devastating maladies of skeletal muscle.

scholarly journals Role of Transforming Growth Factor-β in Skeletal Muscle Fibrosis: A Review

2019 ◽  
Vol 20 (10) ◽  
pp. 2446 ◽  
Author(s):  
Ahmed Ismaeel ◽  
Jeong-Su Kim ◽  
Jeffrey S. Kirk ◽  
Robert S. Smith ◽  
William T. Bohannon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Muscle Fibrosis ◽  
Cellular Processes ◽  
Targeted Treatments ◽  
Skeletal Muscle Fibrosis

Transforming growth factor-beta (TGF-β) isoforms are cytokines involved in a variety of cellular processes, including myofiber repair and regulation of connective tissue formation. Activation of the TGF-β pathway contributes to pathologic fibrosis in most organs. Here, we have focused on examining the evidence demonstrating the involvement of TGF-β in the fibrosis of skeletal muscle particularly. The TGF-β pathway plays a role in different skeletal muscle myopathies, and TGF-β signaling is highly induced in these diseases. In this review, we discuss different molecular mechanisms of TGF-β-mediated skeletal muscle fibrosis and highlight different TGF-β-targeted treatments that target these relevant pathways.

scholarly journals Adipose-Derived Stem Cells Alleviate Radiation-Induced Muscular Fibrosis by Suppressing the Expression of TGF-β1

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Wei Sun ◽  
Xinchu Ni ◽  
Suping Sun ◽  
Leiming Cai ◽  
Jingping Yu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Transforming Growth Factor ◽  
Adipose Derived Stem Cells ◽  
Peripheral Tissues ◽  
Muscle Fibrosis ◽  
Muscle Tissues ◽  
Radiation Induced ◽  
Skeletal Muscle Fibrosis ◽  
Tgf Β1

We aim to investigate the effects of adipose-derived stem cells (ASCs) transplantation on irradiation-induced skeletal muscle fibrosis. Sixty-four rabbits were randomly divided into ASCs group and PBS group followed by irradiation at unilateral hip with a single dose of 80 Gy. Nonirradiated side with normal skeletal muscle served as normal control. Skeletal muscle tissues were collected from eight rabbits in each group at 1 w, 4 w, 8 w, and 26 w after irradiation. Migration of ASCs was observed in the peripheral tissues along the needle passage in the injured muscle. The proportion of the area of collagen fibers to the total area in sections of ASCs group was lower than those of PBS groups at 4 w, 8 w, and 26 w after irradiation. Significant decrease was noted in the integrated optimal density of the transforming growth factorβ1 (TGF-β1) in the ASCs group compared with those of PBS group at 4 w, 8 w, and 26 w after irradiation. Moreover, the expression of TGF-β1 was lower in the ASCs group compared to those of the PBS group at each time point determined by Western blot analysis. ASCs transplantation could alleviate irradiation fibrosis by suppressing the level of TGF-β1 in the irradiated skeletal muscle.

scholarly journals Tenotomy immobilization as a model to investigate skeletal muscle fibrosis (with emphasis on Secreted frizzled-related protein 2)

2016 ◽  
Vol 48 (6) ◽  
pp. 397-408 ◽  
Author(s):  
Uğur Akpulat ◽  
İlyas Onbaşılar ◽  
Y. Çetin Kocaefe
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Transforming Growth Factor ◽  
Fatty Infiltration ◽  
Muscle Fibrosis ◽  
Clear Cut ◽  
Extracellular Matrix Components ◽  
Transcriptional Changes ◽  
Slow Twitch Fibers ◽  
Skeletal Muscle Fibrosis

The pathological endpoint of congenital and senile myopathies is chronic muscle degeneration characterized by the atrophy of contractile elements, accompanied by fibrosis and fatty infiltration of the interstitium. Tenotomy is the release of preload that causes abrupt shortening of the muscle and models atrophy and fibrosis without prominent inflammatory response. Fibrosis in the skeletal muscle is known to be triggered by transforming growth factor (TGF)-β, which is activated by inflammatory events. As these were lacking, tenotomy provided an opportunity to investigate transcriptional events on a background without inflammation. An unbiased look at the transcriptome of tenotomy-immobilized soleus muscle revealed that the majority of the transcriptional changes took place in the first 4 wk. Regarding atrophy, proteasomal and lysosomal pathways were actively involved in accompanying cathepsins and calpains in the breakdown of the macromolecular contractile machinery. The transcriptome provided clear-cut evidence for the upregulation of collagens and several extracellular matrix components that define fibrotic remodeling of the skeletal muscle architecture as well as activation of the fibro-adipogenic precursors. Concomitantly, Sfrp2, a Wnt antagonist as well as a procollagen processor, accompanied fibrosis in skeletal muscle with an expression that was stringently confined to the slow-twitch fibers. An interpreted mechanistic scenario construed the kinetic events initiated through the abnormal shortening of the muscle fibers as enough to trigger the resident latent TGF-β in the extracellular matrix, leading to the activation of fibroadipogenic precursors. As in the heart, Sfrp2 shows itself to be a therapeutic target for the prevention of irreversible fibrosis in degenerative skeletal muscle conditions.

Skeletal muscle fibrosis: the effect of stromal-derived factor-1α-loaded collagen scaffolds

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

scholarly journals Changes in cardiac resident fibroblast physiology and phenotype in aging

2018 ◽  
Vol 315 (4) ◽  
pp. H745-H755 ◽  
Author(s):  
JoAnn Trial ◽  
Katarzyna A. Cieslik
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Cardiac Fibroblasts ◽  
Transforming Growth Factor Β ◽  
Tissue Homeostasis ◽  
Apparent Paradox ◽  
Smad Pathway ◽  
Activated Fibroblasts ◽  
Resident Fibroblast

The cardiac fibroblast plays a central role in tissue homeostasis and in repair after injury. With aging, dysregulated cardiac fibroblasts have a reduced capacity to activate a canonical transforming growth factor-β-Smad pathway and differentiate poorly into contractile myofibroblasts. That results in the formation of an insufficient scar after myocardial infarction. In contrast, in the uninjured aged heart, fibroblasts are activated and acquire a profibrotic phenotype that leads to interstitial fibrosis, ventricular stiffness, and diastolic dysfunction, all conditions that may lead to heart failure. There is an apparent paradox in aging, wherein reparative fibrosis is impaired but interstitial, adverse fibrosis is augmented. This could be explained by analyzing the effectiveness of signaling pathways in resident fibroblasts from young versus aged hearts. Whereas defective signaling by transforming growth factor-β leads to insufficient scar formation by myofibroblasts, enhanced activation of the ERK1/2 pathway may be responsible for interstitial fibrosis mediated by activated fibroblasts. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/fibroblast-phenotypic-changes-in-the-aging-heart/ .

Effects of Geniposide from Gardenia Fruit Pomace on Skeletal-Muscle Fibrosis

2018 ◽  
Vol 66 (23) ◽  
pp. 5802-5811 ◽  
Author(s):  
Haiou Pan ◽  
Yan Li ◽  
Haifeng Qian ◽  
Xiguang Qi ◽  
Gangcheng Wu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Fibrosis ◽  
Fruit Pomace ◽  
Skeletal Muscle Fibrosis
Sign in / Sign up

Export Citation Format

Share Document