scholarly journals MicroRNA Profiling Reveals an Abundant miR-200a-3p Promotes Skeletal Muscle Satellite Cell Development by Targeting TGF-β2 and Regulating the TGF-β2/SMAD Signaling Pathway

2020 ◽  
Vol 21 (9) ◽  
pp. 3274
Author(s):  
Huadong Yin ◽  
Haorong He ◽  
Xiaoxu Shen ◽  
Shuyue Tang ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Muscle Development ◽  
Transforming Growth Factor ◽  
Skeletal Muscle Development ◽  
Developmental Anatomy ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Differentiation And Proliferation

MicroRNAs (miRNAs) are evolutionarily conserved, small noncoding RNAs that play critical post-transcriptional regulatory roles in skeletal muscle development. Chicken is an optimal model to study skeletal muscle formation because its developmental anatomy is similar to that of mammals. In this study, we identified potential miRNAs in the breast muscle of broilers and layers at embryonic day 10 (E10), E13, E16, and E19. We detected 1836 miRNAs, 233 of which were differentially expressed between broilers and layers. In particular, miRNA-200a-3p was significantly more highly expressed in broilers than layers at three time points. In vitro experiments showed that miR-200a-3p accelerated differentiation and proliferation of chicken skeletal muscle satellite cells (SMSCs) and inhibited SMSCs apoptosis. The transforming growth factor 2 (TGF-β2) was identified as a target gene of miR-200a-3p, and which turned out to inhibit differentiation and proliferation, and promote apoptosis of SMSCs. Exogenous TGF-β2 increased the abundances of phosphorylated SMAD2 and SMAD3 proteins, and a miR-200a-3p mimic weakened this effect. The TGF-β2 inhibitor treatment reduced the promotional and inhibitory effects of miR-200a-3p on SMSC differentiation and apoptosis, respectively. Our results indicate that miRNAs are abundantly expressed during embryonic skeletal muscle development, and that miR-200a-3p promotes SMSC development by targeting TGF-β2 and regulating the TGF-β2/SMAD signaling pathway.

scholarly journals ALK5 i II Accelerates Induction of Adipose-Derived Stem Cells toward Schwann Cells through a Non-Smad Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Seiji Sawai ◽  
Tsunao Kishida ◽  
Shin-ichiro Kotani ◽  
Shinji Tsuchida ◽  
Ryo Oda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Schwann Cells ◽  
Transforming Growth Factor ◽  
Specific Inhibitor ◽  
Stem Cell Markers ◽  
Adipose Derived Stem Cells ◽  
Smad Signaling ◽  
Smad Signaling Pathway

Schwann cells (SCs) are likely to be a vital component of cell-based therapies for nerve regeneration. There are various methods for inducing SC-like cells (SCLCs) from adipose-derived stem cells (ADSCs), but their phenotypic and functional characteristics remain unsatisfactory. Here, we report a novel efficient procedure to induce SCLCs by culturing ADSCs with ALK5 inhibitor (ALK5 i) II, a specific inhibitor of activin-like kinase 5 (ALK5) (transforming growth factor-β receptor 1 (TGFβR1)) that is also known as Repsox. The resultant cells that we named “modified SCLCs (mSCLCs)” expressed SC-specific genes more strongly than conventional SCLCs (cSCLCs) and displayed a neurosupportive capacity in vitro, similarly to genuine SCs. Regarding the mechanism of the mSCLC induction by ALK5 i II, knockdown of Smad2 and Smad3, key proteins in the TGFβ/Smad signaling pathway, did not induce SC markers. Meanwhile, expression of multipotent stem cell markers such as Sex-determining region Y- (SRY-) box 2 (Sox2) was upregulated during induction. These findings imply that ALK5 i II exerts its effect via the non-Smad pathway and following upregulation of undifferentiated cell-related genes such as Sox2. The procedure described here results in highly efficient induction of ADSCs into transgene-free and highly functional SCLCs. This approach might be applicable to regeneration therapy for peripheral nerve injury.

scholarly journals Fibromodulin Modulates Chicken Skeletal Muscle Development via the Transforming Growth Factor-β Signaling Pathway

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1477
Author(s):  
Huadong Yin ◽  
Can Cui ◽  
Shunshun Han ◽  
Yuqi Chen ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Matrix Protein ◽  
Muscle Development ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Extracellular Matrix Protein ◽  
Skeletal Muscle Development

Fibromodulin (Fmod), which is an extracellular matrix protein, belongs to the extracellular matrix small-leucine-rich proteoglycan family. Fmod is abundantly expressed in muscles and connective tissues and is involved in biological regulation processes, including cell apoptosis, cell adhesion, and modulation of cytokine activity. Fmod is the main regulator of myostatin, which controls the development of muscle cells, but its regulatory path is unknown. Chicken models are ideal for studying embryonic skeletal muscle development; therefore, to investigate the mechanism of Fmod in muscle development, Fmod-silenced and Fmod-overexpressed chicken myoblasts were constructed. The results showed that Fmod plays a positive role in differentiation by detecting the expression of myogenic differentiation markers, immunofluorescence of MyHC protein, and myotube formation in myoblasts. Fmod regulates expression of atrophy-related genes to alleviate muscle atrophy, which was confirmed by histological analysis of breast muscles in Fmod-modulated chicks in vivo. Additionally, genes differentially expressed between Fmod knockdown and normal myoblasts were enriched in the signaling pathway of transforming growth factor β (TGF-β). Both Fmod-silenced and Fmod-overexpressed myoblasts regulated the expression of TGFBR1 and p-Smad3. Thus, Fmod can promote differentiation but not proliferation of myoblasts by regulating the TGF-β signaling pathway, which may serve a function in muscular atrophy.

scholarly journals Periplaneta Americana Extract may Attenuate 2,4,6-Trinitrobenzenesulfonic Acid-Induced Intestinal Fibrosis by Inhibiting TGF-β/Smad Signaling Pathway

2021 ◽  
Author(s):  
Jing Liu ◽  
Pin Lv ◽  
Xiang Rao ◽  
Jiajia Wang
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Real Time Pcr ◽  
Periplaneta Americana ◽  
Collagen I ◽  
Smad Signaling ◽  
Intestinal Fibrosis ◽  
Smad Signaling Pathway

Abstract PurposeIntestinal fibrosis is an incurable digestive disease accompanied by stricture formation, and it has an increasing incidence in recent years. Periplaneta americana is one of the medicinal insects with a long history. There are few reports on the effect of intestinal fibrosis. This study aims to evaluate the inhibitory effect of PA treatment on intestinal fibrosis. MethodsTNBS was used to establish intestinal fibrosis model by enema in BALB/c mice. The mice were treated with PA (50, 100, 200 mg/kg body weight) and 5-aminosalicylic acid (5-ASA) (40mg/kg) by gavage once a day for 6 weeks. At the end of the last week, the mice were sacrificed. Colon samples were collected for H&E and Masson staining. The mRNA and protein expression of α-smooth muscle actin (α-SMA), collagen I and the transforming growth factor-β (TGF-β) / Smad signaling pathway were conducted by real-time PCR and western blot analysis. In vitro, TGF-β1 was used to induce intestinal fibrosis at human colon fibroblasts (CCD-18Co). And using real-time PCR and western blot methods to detect the expression of α-SMA and collagen I. ResultsPA inhibited the expression of α-SMA and collagen I in vivo and in vitro. But the difference was that PA inhibited the TGF-β/Smad signaling pathway in vivo, and the same results had not been obtained in vitro. Conclusion: PA may attenuate intestinal fibrosis by inhibiting TGF-β/Smad signaling pathway, but more experiments were needed to prove it in vitro. ConclusionsPA has potential pharmacological effects in inhibiting intestinal fibrosis, and the TGF-β/Smad signaling pathway seemed promising.

scholarly journals Targeting TGF-β-Mediated SMAD Signaling Pathway via Novel Recombinant Cytotoxin II: A Potent Protein from Naja naja oxiana Venom in Melanoma

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5148
Author(s):  
Afshin Derakhshani ◽  
Nicola Silvestris ◽  
Nima Hemmat ◽  
Zahra Asadzadeh ◽  
Mahdi Abdoli Shadbad ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Inhibitory Effect ◽  
Melanoma Cells ◽  
Smad Signaling ◽  
Diphenyltetrazolium Bromide ◽  
Smad Signaling Pathway ◽  
Matrix Metallopeptidase ◽  
Tumoral Cells

Since the current treatments have not resulted in the desired outcomes for melanoma patients, there is a need to identify more effective medications. Together with other snake venom proteins, cytotoxin-II has shown promising results in tumoral cells. In this study, recombinant cytotoxin-II (rCTII) was expressed in SHuffle® T7 Express cells, while the epitope mapping of rCTII was performed to reveal the antibody-binding regions of rCTII. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to assess the viability of SK-MEL-3 and HFF-2 cells after treating these cells with rCTII. The qRT-PCR was performed to evaluate the expression levels of matrix metallopeptidase 3 (MMP-3), SMAD2, SMAD3, caspase-8, caspase-9, and miR-214 in order to reveal the rCTII-induced signaling pathways in melanoma. Our results have shown that two regions of amino acids, 6–16 and 19–44, as predicted epitopes of this toxin, are essential for understanding the toxicity of rCTII. Treating the melanoma cells with rCTII substantially inhibited the transforming growth factor-beta (TGF-β)–SMAD signaling pathway and down-regulated the expression of MMP-3 and miR-214 as well. This cytotoxin also restored apoptosis mainly via the intrinsic pathway. The down-regulation of MMP-3 and miR-214 might be associated with the anti-metastatic property of rCTII in melanoma. The inhibitory effect of rCTII on the TGF-β signaling pathway might be associated with increased apoptosis and decreased cancer cell proliferation. It is interesting to see that the IC50 value of rCTII has been lower in the melanoma cells than non-tumoral cells, which may indicate its potential effects as a drug. In conclusion, rCTII, as a novel medication, might serve as a potent and efficient anticancer drug in melanoma.

scholarly journals Inhibition of the JNK/MAPK signaling pathway by myogenesis-associated miRNAs is required for skeletal muscle development

2018 ◽  
Vol 25 (9) ◽  
pp. 1581-1597 ◽  
Author(s):  
Shu-Juan Xie ◽  
Jun-Hao Li ◽  
Hua-Feng Chen ◽  
Ye-Ya Tan ◽  
Shu-Rong Liu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Muscle Development ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Skeletal Muscle Development
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