Smad3 AND Myostatin

Skeletal muscle, comprising a significant proportion (40 to 50 percent) of total body weight in humans, plays a critical role in maintaining normal physiological conditions. Muscle atrophy occurs when the rate of protein degradation exceeds protein synthesis. Sarcopenia refers to age-related muscle atrophy, while cachexia represents a more complex form of muscle wasting associated with various diseases such as cancer, heart failure, and AIDS. Recent research has highlighted the involvement of signaling pathways, including IGF1-Akt-mTOR, MuRF1-MAFbx, and FOXO, in regulating the delicate balance between muscle protein synthesis and breakdown...

Transforming growth factor β (TGF-β) is a pleiotropic cytokine that is widely distributed throughout the body. Its receptor proteins, TGF-β type I and type II receptors, are also ubiquitously expressed. Therefore, the regulation of various signaling outputs in a context-dependent manner is a critical issue in this field. Smad proteins were originally identified as signal-activated transcription factors similar to signal transducer and activator of transcription proteins. Smads are activated by serine phosphorylation mediated by intrinsic receptor dual specificity kinases of the TGF-β family, indicating that Smads are receptor-restricted effector molecules downstream of ligands of the TGF-β family...

BACKGROUND: Myostatin (MSTN) inhibition has demonstrated promise for the treatment of diseases associated with muscle loss. In a previous study, we discovered that Glycyrrhiza uralensis (G. uralensis) crude water extract (CWE) inhibits MSTN expression while promoting myogenesis. Furthermore, three specific compounds of G. uralensis, namely liquiritigenin, tetrahydroxymethoxychalcone, and Licochalcone B (Lic B), were found to promote myoblast proliferation and differentiation, as well as accelerate the regeneration of injured muscle tissue...

Myostatin (growth differentiation factor 8) is a member of the transforming growth factor-β superfamily. It is secreted mostly by skeletal muscles, although small amounts of myostatin are produced by the myocardium and the adipose tissue as well. Myostatin binds to activin IIB membrane receptors to activate the downstream intracellular canonical Smad2/Smad3 pathway, and additionally acts on non-Smad (non-canonical) pathways. Studies on transgenic animals have shown that overexpression of myostatin reduces the heart mass, whereas removal of myostatin has an opposite effect...

The purpose of the present study was to determine the effects of obesity and biological sex on myostatin expression in humans, and to examine the direct effects of myostatin, SMAD2 and SMAD3 on insulin signaling in primary human skeletal muscle cells (HSkMCs). Cohort 1: Fifteen lean (BMI: 22.1 ± 0.5 kg/m2 , n=8 males, n=7 females) and fourteen obese (BMI: 40.6 ± 1.4 kg/m2 , n=7 males, n=7 females) individuals underwent skeletal muscle biopsies and an oral glucose tolerance test (OGTT). Cohort 2: Fifteen young lean (BMI: 22...

Glucocorticoids (GCs) administration, such as cortisol acetate (CA) and dexamethasone (DEXA), is used worldwide due to their anti-inflammatory, anti-allergic, and immunosuppressive properties. However, muscle atrophy is one of the primary deleterious induced responses from the chronic treatment with GCs since it stimulates muscle degradation inhibiting muscle protein synthesis. Animal models allow a better understanding of the molecular pathways involved in this process of gene modulation and production of hypertrophic and atrophic proteins...

This article focuses on deciphering the effect of myostatin (MSTN) on podocyte apoptosis in membranous nephropathy (MN) and fathoming out its underlying mechanism. Rats received the intravenous injection of cationized-bovine serum albumin to induce MN in vivo , while angiotensin II (Ang II) was exposed to AB8/13 cells to induce MN model in vitro . The mRNA expression of MSTN was detected by qRT-PCR. The effects of MSTN silencing on MN model rats and cells were assessed by cell counting kit-8 assay, flow cytometry, hematoxylin and eosin staining, and TUNEL assay...

Cancer-derived exosomes are involved in the development of cancer cachexia. Carnosol, which exhibited ameliorating effects on cancer cachexia of C26 tumour-bearing mice in our previous study, alleviated atrophy of C2C12 myotubes induced by exosomes of C26 tumour cells in the present study. MiR-183-5p was found to be rich in C26 cells and C26 exosomes, and miR-183-5p mimic could directly induce atrophy of C2C12 myotubes. Carnosol at 5 to 20 μM could dose-dependently ameliorate the myotube atrophy induced by miR-183-5p...

Skeletal muscle mass is negatively regulated by several TGF-β superfamily members. Myostatin (MSTN) is the most prominent negative regulator of muscle mass. Recent studies show that in addition to MSTN, GDF11, which shares high sequence identity with MSTN, induces muscle atrophy in vitro and in vivo at supraphysiological levels, whereas controversy regarding its roles exists. Furthermore, higher circulating GDF11 levels associate with frailty in humans. On the other hand, little is known about the effect of pathophysiological levels of GDF11 on muscle atrophy...

Skeletal muscle dysfunction is an important extrapulmonary comorbidity of chronic obstructive pulmonary disease (COPD). Muscle-derived cytokines (myokines) play important roles in skeletal muscle growth and function, but their contributions to skeletal muscle dysfunction in COPD have not been fully understood. In the current study, by using a well-established mouse model of COPD with skeletal muscle dysfunction, we found that the expressions of Fndc5 (fibronectin type III domain-containing protein 5, the precursor of irisin) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) were decreased, while myostatin (Mstn), phosphorylated extracellular regulated kinase (p-Erk1/2), and p-Smad3 expressions were upregulated in skeletal muscles from cigarette smoke-exposed mice and in cigarette smoke extract (CSE)-stimulated C2C12 myotubes...

BACKGROUND: Nutrient regulation has been proven to be an effective way to improve the flesh quality in fish. As a necessary nutrient for fish growth, protein accounts for the highest proportion in the fish diet and is expensive. Although our team found that the effect of protein on the muscle hardness of grass carp was probably related to an increased collagen content, the mechanism for this effect has not been deeply explored. Moreover, few studies have explored the protein requirements of sub-adult grass crap (Ctenopharyngodon idella)...

Myostatin ( Mstn ) is known as growth/differentiation factor-8 (GDF-8). Knockout or knockdown of Mstn gene promotes muscle development and reduces fat content. Here we prepared Mstn knockdown mice by RNA interference, then the morphology of the skeletal muscle, the content of triglyceride (TG), the content and composition of fatty acids in the skeletal muscle were detected. The expression of Mstn reduced in muscle of Mstn knockdown mice compared to the controls. The cross sectional areas of the skeletal muscle myofibers were significantly larger while the content of TG was less than that of the controls, and the ratios of n-3 / n-6 and unsat/sat in the knockdown mice increased significantly...

Myostatin (MSTN), a member of the TGF-β superfamily, negatively regulates muscle growth. MSTN inhibition has been known to cause a double-muscled phenotype in skeletal muscle and fibrosis reduction in the heart. However, the role of MSTN in the cardiac extracellular matrix (ECM) needs more studies in various species of animal models to draw more objective conclusions. The main objective of the present study was to investigate whether loss of MSTN affects the cardiac extracellular matrix in pigs. Three MSTN knockouts (MSTN-/-) and three wild type (WT) male pigs were generated by crossing MSTN ± heterozygous gilts and boars...

Aim: The present study aimed to analyze the role of myokines and the regeneration capacity of skeletal muscle during chronic hypobaric hypoxia (HH). Method : Male SD rats were exposed to HH for 1d, 3d, and 7d. Results: Exposure to HH enhanced the levels of decorin, irisin, IL-6 and IL-15 till 3 days of hypoxia and on 7 day of exposure, no significant changes were observed in relation to control. A significant upregulation in myostatin, AMPK, SMAD3, SMAD4, FOXO-1, MURF-1 expression was observed with prolonged HH exposure as compared to normoxic control...

Epinephelus coioides is a fish species with high economic value due to its delicious meat, high protein content, and rich fatty acid nutrition. It has become a high-economic fish in southern parts of China and some other Southeast Asian countries. In this study, the myostatin nucleic acid vaccine was constructed and used to immunize E. coioides . The results from body length and weight measurements indicated the myostatin nucleic acid vaccine promoted E. coioides growth performance by increasing muscle fiber size...

Heat stress has an adverse effect on the development of poultry farming, which has always aroused great concern. This study was carried out to investigate the protein breakdown mechanism responsible for the suppressive effect of constant heat stress on muscle growth in growing broilers. A total of 96, 29-day-old, Arbor Acres male broilers were randomly divided into two groups, a thermoneutral control (21 ± 1 °C, TC) and a heat stress (31 ± 1 °C, HS) group, with six replicates in each group and eight birds in each replicate...

Coffee has been shown to attenuate sarcopenia, the age-associated muscle atrophy. Myostatin (MSTN), a member of the TGF-β growth/differentiation factor superfamily, is a potent negative regulator of skeletal muscle mass, and MSTN-inhibition increases muscle mass or prevents muscle atrophy. This study, thus, investigated the presence of MSTN-inhibitory capacity in coffee extracts. The ethanol-extract of coffee silverskin (CSE) but not other extracts demonstrated anti-MSTN activity in a pGL3-(CAGA)12 -luciferase reporter gene assay...

SMAD2 is a transcription factor, the activity of which is regulated by members of the transforming growth factor β (TGFβ) superfamily. Although activation of SMAD2 and SMAD3 downstream of TGFβ or myostatin signaling is known to inhibit myogenesis, we found that SMAD2 in the absence of TGFβ signaling promotes terminal myogenic differentiation. We found that, during myogenic differentiation, SMAD2 expression is induced. Knockout of SMAD2 expression in primary myoblasts did not affect the efficiency of myogenic differentiation but produced smaller myotubes with reduced expression of the terminal differentiation marker myogenin...

OBJECTIVE: To explore the effect of berberine (BBR) on skeletal muscle mass and metabolism and the possible mechanism. METHODS: Eight-week-old male C57BL/6 mice were fed with a high-fat diet (HFD) for 8 weeks to establish the insulin resistance obesity model. Then, mice were randomly divided into two groups (normal chow diet (NCD) and HFD), while NCD and HFD were further classified into two groups respectively, which were NCD+CS (Carmellose Sodium), NCD+BBR, HFD+CS and HFD+BBR...

Inhibition of myostatin- and activin-mediated SMAD2/3 signaling using ligand traps, such as soluble receptors, ligand-targeting propeptides and antibodies, or follistatin can increase skeletal muscle mass in healthy mice and ameliorate wasting in models of cancer cachexia and muscular dystrophy. However, clinical translation of these extracellular approaches targeting myostatin and activin has been hindered by the challenges of achieving efficacy without potential effects in other tissues. Toward the goal of developing tissue-specific myostatin/activin interventions, we explored the ability of transmembrane prostate androgen-induced (TMEPAI), an inhibitor of transforming growth factor-β (TGF-β1)-mediated SMAD2/3 signaling, to promote growth, and counter atrophy, in skeletal muscle...