Molecular Therapy-Nucleic Acids
·
2023
·
IF 8.8
Xinyi Gu,Shen Wang,Dongdong Li,Bo Jin,Zhidan Qi,Jin Deng,Chen Huang,Xiaofeng Yin
Peripheral nerve injury can lead to progressive muscle atrophy and poor motor function recovery, which is a difficult point of treatment, and the mechanism needs to be further explored. In previous studies we found that miR-142a-3p was significantly upregulated and persistently high expressed in denervated mouse skeletal muscle. Here, we show that overexpression of miR-142a-3p inhibited the growth and differentiation of C2C12 myoblast, while knockdown of miR-142a-3p had a promoting effect. In vitro, knockdown of miR-142a-3p in denervated mouse skeletal muscle effectively increased proliferating muscle satellite cells and ameliorated muscle atrophy. Mechanistically, the myoregulator Mef2a was proved to be an important downstream target of miR-142a-3p, and miR-142a-3p regulates skeletal muscle differentiation and regeneration by inhibiting the expression of Mef2a. The co-knockdown of Mef2a and miR-142a-3p effectively alleviated or offset the biological effects of miR-142a-3p knockdown. In conclusion, our data revealed that miR-142a-3p regulates neurogenic skeletal muscle atrophy by targeting Mef2a.
研究领域:
神经科学
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分子生物学
·
肌肉骨骼疾病
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2017
·
IF 2.466
Fan Chen,Dandan Chen,Yubin Zhang,Liang Jin,Han Zhang,Miyang Wan,Tianshu Pan,Xiaochuan Wang,Yuheng Su,Yitao Xu,Junmei Ye
Interleukin-6 (IL-6) signaling is critical for cardiomyocyte hypertrophy, while the role of IL-6 in the pathogenesis of myocardium hypertrophy remains controversial. To determine the essential role of IL-6 signaling for the cardiac development during AngII-induced hypertension, and to elucidate the mechanisms, wild-type (WT) and IL-6 knockout (IL-6 KO) mice were infused subcutaneously with either vehicle or AngII (1.5 μg/h/mouse) for 1 week. Immunohistological and serum studies revealed that the extents of cardiac fibrosis, inflammation and apoptosis were reduced in IL-6 KO heart during AngII-stimulation, while cardiac hypertrophy was obviously induced. To investigate the underlying mechanisms, by using myocardial tissue and neonatal cardiomyocytes, we observed that IL-6/STAT3 signaling was activated under the stimulation of AngII both in vivo and in vitro . Further investigation suggested that STAT3 activation enhances the inhibitory effect of EndoG on MEF2A and hampers cardiomyocyte hypertrophy. Our study is the first to show the important role of IL-6 in regulating cardiac pathogenesis via inflammation and apoptosis during AngII-induced hypertension. We also provide a novel link between IL-6/STAT3 and EndoG/MEF2A pathway that affects cardiac hypertrophy during AngII stimulation.
研究领域:
心脏病学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Biology Direct
·
2026
·Vol. 21
·期 1
·177
·
IF 5.5
Sun Tian-qi,Wu Shuo,Qiao Jing,Liang Gang,Liu Chao-feng,Jiang Hui-yu,Liu Kai-yuan,Wang Hai-long,Pang Min
Non‑small cell lung cancer (NSCLC), particularly lung adenocarcinoma (LUAD), exhibits a high rate of primary resistance to immune checkpoint inhibitors, underscoring the need to decipher the molecular mechanisms of immune evasion. Here, we identify ANKRD49 as a critical regulator of PD‑L1 expression and immunosuppression in LUAD. Immunohistochemical analysis of clinical LUAD specimens revealed that high ANKRD49 expression correlates with reduced CD4 + and CD8 + T cell infiltration, increased FOXP3 + regulatory T cells, and elevated PD‑L1 levels. Functional experiments demonstrated that ANKRD49 overexpression in LUAD cells suppresses T cell cytotoxicity, promotes T cell apoptosis, and impairs granzyme B and IFN‑γ production in vitro. Mechanistically, ANKRD49 directly binds the transcription factor MEF2A via its second ankyrin repeat domain, upregulates MEF2A expression, and promotes its transcriptional activity at two specific sites within the PD‑L1 promoter. Chromatin immunoprecipitation and luciferase reporter assays confirmed that MEF2A directly activates PD‑L1 transcription in an ANKRD49‑dependent manner. In subcutaneous and metastatic mouse models, ANKRD49 overexpression accelerates tumor growth and metastasis, while PD‑L1 blockade reverses these effects and restores antitumor immunity. Collectively, our findings establish the ANKRD49–MEF2A–PD‑L1 axis as a novel driver of immune evasion in LUAD, and identify ANKRD49 ankyrin repeat domain 2 as a potential therapeutic target for overcoming immunotherapy resistance.
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DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2017
·
IF 2.466
Dandan Chen,Fan Chen,Yitao Xu,Yubin Zhang,Zhe Li,Han Zhang,Tianshu Pan,Yuheng Su,Miyang Wan,Xiaochuan Wang,Junmei Ye
Protein kinase B2 (AKT2) is implicated in diverse process of cardiomyocyte signaling including survival and metabolism. However, the role of AKT2 in myocardium development and the signaling pathway is rarely understood. Therefore, we sought to determine the effect of AKT2 deletion on heart development and its downstream targets. By using experimental animal models and neonatal rat cardiomyocytes (NRCMs), we observed that AKT2 deficiency induces retardation of heart development and increased systemic blood pressure (BP) without affecting cardiac function. Further investigation suggested that deficiency of AKT2 in myocardium results in diminished MEF2A abundance, which induced decreased size of cardiomyocytes. We additionally confirmed that EndoG , which is also regulated by AKT2, is a suppressor of MEF2A in myocardium. Finally, our results proved that AKT2 deficiency impairs the response to β-adrenergic stimuli that normally causes hypertrophy in cardiomyocytes by downregulating MEF2A expression. Our data are the first to show the important role of AKT2 in determining the size of myocardium, its deficiency causes retardation of cardiomyocyte development. We also proved a novel pathway of heart development involving EndoG and MEF2A regulated by AKT2.
研究领域:
心脏病学
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分子生物学
·
发育生物学
✓ 已验证
DOI
PubMed
高影响因子
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