CELLULAR SIGNALLING
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2025
·
IF 3.7
Biao-Hu Quan,Xin-Yue Liu,Zhou-Yan Li,Sheng-Zhong Han,Qi-Chao Cui,Shuang-Yan Chang,Si-Tong Lv,Xi-Jun Yin,Shuang Liang
Pulmonary fibrosis is a chronic interstitial lung disease characterized by irreversible, progressive lung scarring and eventual respiratory failure. Fibroblast activation plays a crucial role in the progression of pulmonary fibrosis. Transforming growth factor-β (TGF-β) signaling contributes to pulmonary fibrosis by regulating lung fibroblast activation. Currently, most studies focus on TGF-β1 regulatory effects on fibroblasts, with limited reports on myostatin (MSTN), another member of the same family. This study used MSTN gene knockout (MSTN −/− ) boars as animal models to explore MSTN regulatory effects on pulmonary fibrosis by modulating lung fibroblast activation. Studies have demonstrated that MSTN is significantly upregulated in the lungs during pulmonary fibrosis, promoting the activation of downstream Smad and AKT signaling pathways. MSTN −/− inhibits alveolar collapse and interstitial thickening in pulmonary fibrosis pigs and suppresses downstream Smad and AKT signaling. In vitro experiments showed that MSTN −/− inhibits lung fibroblast activation by blocking Smad/AKT signaling. These findings suggest that the MSTN/Smad/AKT signaling axis suppresses pulmonary fibrosis by inhibiting lung fibroblast activation, indicating that MSTN could be a potential therapeutic target for pulmonary fibrosis.
研究领域:
分子生物学
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医学
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DOI
PubMed
高影响因子
Communications Biology
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2020
·Vol. 3
·期 1
·1-15
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IF 4.165
Ren Hongyan,Xiao Wei,Qin Xingliang,Cai Gangzhi,Chen Hao,Hua Zaidong,Cheng Cheng,Li Xinglei,Hua Wenjun,Xiao Hongwei,Zhang Liping,Dai Jiali,Zheng Xinmin,Zhu Zhe,Qian Chong,Yao Jie,Bi Yanzhen
Myostatin (MSTN), associated with the “double muscling” phenotype, affects muscle growth and fat deposition in animals, whereas how MSTN affects adipogenesis remains to be discovered. Here we show that MSTN can act through the MEF2C/miR222/SCD5 cascade to regulate fatty acid metabolism. We generated MSTN-knockout (KO) cloned Meishan pigs, which exhibits typical double muscling trait. We then sequenced transcriptome of subcutaneous fat tissues of wild-type (WT) and MSTN-KO pigs, and intersected the differentially expressed mRNAs and miRNAs to predict that stearoyl-CoA desaturase 5 (SCD5) is targeted by miR222. Transcription factor binding prediction showed that myogenic transcription factor 2C (MEF2C) potentially binds to the miR222 promoter. We hypothesized that MSTN-KO upregulates MEF2C and consequently increases the miR222 expression, which in turn targets SCD5 to suppress its translation. Biochemical, molecular and cellular experiments verified the existence of the cascade. This novel molecular pathway sheds light on new targets for genetic improvements in pigs.
研究领域:
动物遗传学
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分子生物学
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动物科学
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产品关联
DOI
PubMed
高影响因子
eLife
·
2023
·
IF 7.7
Zhao-Bo Luo,Shengzhong Han,Xi-Jun Yin,Hongye Liu,Junxia Wang,Meifu Xuan,Chunyun Hao,Danqi Wang,Yize Liu,Shuangyan Chang,Dongxu Li,Kai Gao,Huiling Li,Biaohu Quan,Lin-Hu Quan,Jin-Dan Kang
The host genome may influence the composition of the intestinal microbiota, and the intestinal microbiota has a significant effect on muscle growth and development. In this study, we found that the deletion of the myostatin (MSTN) gene positively regulates the expression of the intestinal tight junction-related genes TJP1 and OCLN through the myosin light-chain kinase/myosin light chain pathway. The intestinal structure of MSTN−/− pigs differed from wild-type, including by the presence of a thicker muscularis and longer plicae. Together, these changes affect the structure of intestinal microbiota. Mice transplanted with the intestinal microbiota of MSTN−/− pigs had myofibers with larger cross-sectional areas and higher fast-twitch glycolytic muscle mass. Microbes responsible for the production of short-chain fatty acids (SCFAs) were enriched in both the MSTN−/− pigs and recipient mice, and SCFAs levels were elevated in the colon contents. We also demonstrated that valeric acid stimulates type IIb myofiber growth by activating the Akt/mTOR pathway via G protein-coupled receptor 43 and ameliorates dexamethasone-induced muscle atrophy. This is the first study to identify the MSTN gene-gut microbiota-SCFA axis and its regulatory role in fast-twitch glycolytic muscle growth.
研究领域:
遗传学
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微生物学
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肌肉生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
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2022
·
IF 6.064
Zheng Ya,Chen Juanjuan,Wang Xiaoxuan,Han Ling,Yang Yayuan,Wang Qi,Yu Qunli
Gut microbiome and heredity are two important factors affecting the intramuscular fat (IMF) of cattle, excluding age, sex, and nutrition. This study aimed at deciphering these two differences by analyzing the gut microbiome and intramuscular differentially expressed genes (DEGs) in the Angus and Chinese Simmental cattle. Feces and longissimus dorsi were collected from the two groups of animals (n = 20/group) for multiomics analysis. Angus holds a significantly higher diversity than Chinese Simmental, and the relative abundance of Roseburia, Prevotella, Coprococcus, etc., was obviously higher in Angus. Chinese Simmental had higher levels of isobutyrate, isovalerate, and valerate, although similar levels of acetate, propionate, and butyrate were observed for the two groups. The DEGs upregulated in Chinese Simmental were mainly involved in immune and inflammatory responses, while those in Angus were associated with the regulation of muscle system and myofibril. We finally identified 17 species, including Eubacterium rectale, etc., which were positively correlated to muscle and fat metabolism genes (MSTN, MYLPF, TNNT3, and FABP3/4) and illustrate the associations between them. Our study unveils the gut microbial differences and significant DEGs as well as their associations between the two breeds, providing valuable guidance for future mechanism research and development of intervention strategies to improve meat quality.
研究领域:
动物科学
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微生物学
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基因组学
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营养学
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DOI
PubMed
高影响因子
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