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262 results on '"Chen, Jinghai"'

2. Flavin Containing Monooxygenase 2 Prevents Cardiac Fibrosis via CYP2J3-SMURF2 Axis.

Author

Ni, Cheng, Chen, Yongjian, Xu, Yinchuan, Zhao, Jing, Li, Qingju, Xiao, Changchen, Wu, Yan, Wang, Jingyi, Wang, Yingchao, Zhong, Zhiwei, Zhang, Ling, Wu, Rongrong, Liu, Qingnian, Wu, Xianpeng, Ke, Changle, Zhu, Wei, Chen, Jinghai, Huang, Jijun, Wang, Yibin, Wang, Jianan, and Hu, Xinyang

Subjects
cytosol, downregulation, fibrosis, humans, myocardial infarction
Abstract

BACKGROUND: Cardiac fibrosis is a common pathological feature associated with adverse clinical outcome in postinjury remodeling and has no effective therapy. Using an unbiased transcriptome analysis, we identified FMO2 (flavin-containing monooxygenase 2) as a top-ranked gene dynamically expressed following myocardial infarction (MI) in hearts across different species including rodents, nonhuman primates, and human. However, the functional role of FMO2 in cardiac remodeling is largely unknown. METHODS: Single-nuclei transcriptome analysis was performed to identify FMO2 after MI; FMO2 ablation rats were generated both in genetic level using the CRISPR-cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9) technology and lentivirus-mediated manner. Gain-of-function experiments were conducted using postn-promoter FMO2, miR1a/miR133a-FMO2 lentivirus, and enzymatic activity mutant FMO2 lentivirus after MI. RESULTS: A significant downregulation of FMO2 was consistently observed in hearts after MI in rodents, nonhuman primates, and patients. Single-nuclei transcriptome analysis showed cardiac expression of FMO2 was enriched in fibroblasts rather than myocytes. Elevated spontaneous tissue fibrosis was observed in the FMO2-null animals without external stress. In contrast, fibroblast-specific expression of FMO2 markedly reduced cardiac fibrosis following MI in rodents and nonhuman primates associated with diminished SMAD2/3 phosphorylation. Unexpectedly, the FMO2-mediated regulation in fibrosis and SMAD2/3 signaling was independent of its enzymatic activity. Rather, FMO2 was detected to interact with CYP2J3 (cytochrome p450 superfamily 2J3). Binding of FMO2 to CYP2J3 disrupted CYP2J3 interaction with SMURF2 (SMAD-specific E3 ubiquitin ligase 2) in cytosol, leading to increased cytoplasm to nuclear translocation of SMURF2 and consequent inhibition of SMAD2/3 signaling. CONCLUSIONS: Loss of FMO2 is a conserved molecular signature in postinjury hearts. FMO2 possesses a previously uncharacterized enzyme-independent antifibrosis activity via the CYP2J3-SMURF2 axis. Restoring FMO2 expression exerts potent ameliorative effect against fibrotic remodeling in postinjury hearts from rodents to nonhuman primates. Therefore, FMO2 is a potential therapeutic target for treating cardiac fibrosis following injury.

Published
2022

11. Cardiac CIP protein regulates dystrophic cardiomyopathy

Author

He, Xin, Liu, Jianming, Gu, Fei, Chen, Jinghai, Lu, Yao Wei, Ding, Jian, Guo, Haipeng, Nie, Mao, Kataoka, Masaharu, Lin, Zhiqiang, Hu, Xiaoyun, Chen, Huaqun, Liao, Xinxue, Dong, Yugang, Min, Wang, Deng, Zhong-Liang, Pu, William T., Huang, Zhan-Peng, and Wang, Da-Zhi

Published
2022
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12. Long noncoding RNA Cfast regulates cardiac fibrosis

Author

Zhang, Feng, Fu, Xuyang, Kataoka, Masaharu, Liu, Ning, Wang, Yingchao, Gao, Feng, Liang, Tian, Dong, Xiaoxuan, Pei, Jianqiu, Hu, Xiaoyun, Zhu, Wei, Yu, Hong, Cowan, Douglas B., Hu, Xinyang, Huang, Zhan-Peng, Wang, Jian’an, Wang, Da-Zhi, and Chen, Jinghai

Published
2021
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13. Ferroptosis as a target for protection against cardiomyopathy

Author

Fang, Xuexian, Wang, Hao, Han, Dan, Xie, Enjun, Yang, Xiang, Wei, Jiayu, Gu, Shanshan, Gao, Feng, Zhu, Nali, Yin, Xiangju, Cheng, Qi, Zhang, Pan, Dai, Wei, Chen, Jinghai, Yang, Fuquan, Yang, Huang-Tian, Linkermann, Andreas, Gu, Wei, Min, Junxia, and Wang, Fudi

Published
2019

16. LncRNA LncHrt preserves cardiac metabolic homeostasis and heart function by modulating the LKB1-AMPK signaling pathway

Author

Liu, Ning, Kataoka, Masaharu, Wang, Yingchao, Pu, Linbin, Dong, Xiaoxuan, Fu, Xuyang, Zhang, Feng, Gao, Feng, Liang, Tian, Pei, Jianqiu, Xiao, Changchen, Qiu, Qiongzi, Hong, Tingting, Chen, Qiming, Zhao, Jing, Zhu, Lianlian, He, Junhua, Hu, Xiaoyun, Nie, Yu, Zhu, Wei, Yu, Hong, Cowan, Douglas B., Hu, Xinyang, Wang, Jian’an, Wang, Da-Zhi, and Chen, Jinghai

Published
2021
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17. FMO2 ameliorates nonalcoholic fatty liver disease by suppressing ER-to-Golgi transport of SREBP1

Author

Ke, Changle, primary, Xiao, Changchen, additional, Li, Jiamin, additional, Wu, Xianpeng, additional, Zhang, Yu, additional, Chen, Yongjian, additional, Sheng, Shuyuan, additional, Fu, Zaiyang, additional, Wang, Lingjun, additional, Ni, Cheng, additional, Zhao, Jing, additional, Shi, Yanna, additional, Wu, Yan, additional, Zhong, Zhiwei, additional, Nan, Jinliang, additional, Zhu, Wei, additional, Chen, Jinghai, additional, Wu, Rongrong, additional, and Hu, Xinyang, additional

Published
2023
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19. A novel chaperone flavin-containing monooxygenase 2 confers cardioprotection against ischemia through its disulfide-bond catalytic activity

Author

Liu, Qingnian, primary, Huang, Jiniu, additional, Ding, Hao, additional, Tao, Yue, additional, Xiao, Changchen, additional, Wang, Yingchao, additional, Wu, Rongrong, additional, Ni, Cheng, additional, Zhong, Zhiwei, additional, Zhu, Wei, additional, Chen, Jinghai, additional, Zhang, Chenyun, additional, Hu, Xinyang, additional, and Wang, Jian’an, additional

Published
2023
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23. Adapting cytoskeleton-mitochondria patterning with myocyte differentiation by promyogenic PRR33

Author

Fu, Xuyang, Zhang, Feng, Dong, Xiaoxuan, Pu, Linbin, Feng, Yan, Xu, Yang, Gao, Feng, Liang, Tian, Kang, Jianmeng, Sun, Hongke, Hong, Tingting, Liu, Yunxia, Zhou, Hongmei, Jiang, Jun, Yin, Deling, Hu, Xinyang, Wang, Da-Zhi, Ding, Jian, and Chen, Jinghai

Abstract

Coordinated cytoskeleton-mitochondria organization during myogenesis is crucial for muscle development and function. Our understanding of the underlying regulatory mechanisms remains inadequate. Here, we identified a novel muscle-enriched protein, PRR33, which is upregulated during myogenesis and acts as a promyogenic factor. Depletion of Prr33in C2C12 represses myoblast differentiation. Genetic deletion of Prr33in mice reduces myofiber size and decreases muscle strength. The Prr33mutant mice also exhibit impaired myogenesis and defects in muscle regeneration in response to injury. Interactome and transcriptome analyses reveal that PRR33 regulates cytoskeleton and mitochondrial function. Remarkably, PRR33 interacts with DESMIN, a key regulator of cytoskeleton-mitochondria organization in muscle cells. Abrogation of PRR33 in myocytes substantially abolishes the interaction of DESMIN filaments with mitochondria, leading to abnormal intracellular accumulation of DESMIN and mitochondrial disorganization/dysfunction in myofibers. Together, our findings demonstrate that PRR33 and DESMIN constitute an important regulatory module coordinating mitochondrial organization with muscle differentiation.

Published
2024
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27. FMO2 (Flavin Containing Monooxygenase 2) Prevents Cardiac Fibrosis via CYP2J3-SMURF2 Axis

Author

Ni, Cheng, primary, Chen, Yongjian, additional, Xu, Yinchuan, additional, Zhao, Jing, additional, Li, Qingju, additional, Xiao, Changchen, additional, Wu, Yan, additional, Wang, Jingyi, additional, Wang, Yingchao, additional, Zhong, Zhiwei, additional, Zhang, Ling, additional, Wu, Rongrong, additional, Liu, Qingnian, additional, Wu, Xianpeng, additional, Ke, Changle, additional, Zhu, Wei, additional, Chen, Jinghai, additional, Huang, Jijun, additional, Wang, Yibin, additional, Wang, Jian’an, additional, and Hu, Xinyang, additional

Published
2022
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29. Cardiomyocyte-enriched protein CIP protects against pathophysiological stresses and regulates cardiac homeostasis

Author

Huang, Zhan-Peng, Kataoka, Masaharu, Chen, Jinghai, Wu, Gengze, Ding, Jian, Nie, Mao, Lin, Zhiqiang, Liu, Jianming, Hu, Xiaoyun, Ma, Lixin, Zhou, Bin, Wakimoto, Hiroko, Zeng, Chunyu, Kyselovic, Jan, Deng, Zhong-Liang, Seidman, Christine E., Seidman, J.G., Pu, William T., and Wang, Da-Zhi

Subjects
Heart diseases -- Genetic aspects -- Development and progression, Gene mutations -- Health aspects, Gene expression -- Health aspects, Cardiomyopathy -- Genetic aspects -- Development and progression, Health care industry
Abstract

Cardiomyopathy is a common human disorder that is characterized by contractile dysfunction and cardiac remodeling. Genetic mutations and altered expression of genes encoding many signaling molecules and contractile proteins are associated with cardiomyopathy; however, how cardiomyocytes sense pathophysiological stresses in order to then modulate cardiac remodeling remains poorly understood. Here, we have described a regulator in the heart that harmonizes the progression of cardiac hypertrophy and dilation. We determined that expression of the myocyte-enriched protein cardiac ISL1- interacting protein (CIP, also known as MLIP) is reduced in patients with dilated cardiomyopathy. As CIP is highly conserved between human and mouse, we evaluated the effects of CIP deficiency on cardiac remodeling in mice. Deletion of the CIP-encoding gene accelerated progress from hypertrophy to heart failure in several cardiomyopathy models. Conversely, transgenic and AAV-mediated CIP overexpression prevented pathologic remodeling and preserved cardiac function. CIP deficiency combined with lamin A/C deletion resulted in severe dilated cardiomyopathy and cardiac dysfunction in the absence of stress. Transcriptome analyses of CIP-deficient hearts revealed that the p53- and FOXO1-mediated gene networks related to homeostasis are disturbed upon pressure overload stress. Moreover, FOXO1 overexpression suppressed stress-induced cardiomyocyte hypertrophy in CIP-deficient cardiomyocytes. Our studies identify CIP as a key regulator of cardiomyopathy that has potential as a therapeutic target to attenuate heart failure progression., Introduction Cardiovascular diseases continue to be leading causes of death and disability. Despite this alarming fact, there is a lack of effectual treatment, and the molecular mechanisms underlying these devastating [...]

Published
2015
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30. Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies

Author

Wang, Gang, McCain, Megan L., Yang, Luhan, He, Aibin, Pasqualini, Francesco Silvio, Agarwal, Ashutosh, Yuan, Hongyan, Jiang, Dawei, Zhang, Donghui, Zangi, Lior, Geva, Judith, Roberts, Amy E., Ma, Qing, Ding, Jian, Chen, Jinghai, Wang, Da-Zhi, Li, Kai, Wang, Jiwu, Wanders, Ronald J.A., Kulik, Wim, Vaz, Frederic M., Laflamme, Michael A., Murry, Charles E., Chien, Kenneth R., Kelley, Richard I., Church, George M., Parker, Kevin Kit, and Pu, William T.

Subjects
Barth syndrome -- Complications and side effects -- Development and progression -- Research, Heart diseases -- Risk factors -- Development and progression -- Genetic aspects -- Research, Stem cells -- Physiological aspects -- Genetic aspects -- Research, Cardiomyopathy -- Risk factors -- Development and progression -- Genetic aspects -- Research, Biological sciences, Health
Abstract

Study of monogenic mitochondrial cardiomyopathies may yield insights into mitochondrial roles in cardiac development and disease. Here, we combined patient-derived and genetically engineered induced pluripotent stem cells (iPSCs) with tissue engineering to elucidate the pathophysiology underlying the cardiomyopathy of Barth syndrome (BTHS), a mitochondrial disorder caused by mutation of the gene encoding tafazzin (TAZ). Using BTHS iPSC-derived cardiomyocytes (iPSC-CMs), we defined metabolic, structural and functional abnormalities associated with TAZ mutation. BTHS iPSC-CMs assembled sparse and irregular sarcomeres, and engineered BTHS 'heart-on-chip' tissues contracted weakly. Gene replacement and genome editing demonstrated that TAZ mutation is necessary and sufficient for these phenotypes. Sarcomere assembly and myocardial contraction abnormalities occurred in the context of normal whole-cell ATP levels. Excess levels of reactive oxygen species mechanistically linked TAZ mutation to impaired cardiomyocyte function. Our study provides new insights into the pathogenesis of Barth syndrome, suggests new treatment strategies and advances iPSC-based in vitro modeling of cardiomyopathy., BTHS is an X-linked cardiac and skeletal mitochondrial myopathy caused by mutation of the gene encoding tafazzin (1), an acyltransferase responsible for normal acylation of cardiolipin, the major phospholipid of [...]

Published
2014
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31. GDF11 enhances therapeutic functions of mesenchymal stem cells for angiogenesis

Author

Zhang, Chi, Lin, Yinuo, Zhang, Ke, Meng, Luyang, Hu, Xinyang, Chen, Jinghai, Zhu, Wei, and Yu, Hong

Subjects
Medicine (General), Research, Endothelial cells, Neovascularization, Physiologic, Mesenchymal Stem Cells, QD415-436, Mesenchymal Stem Cell Transplantation, Biochemistry, Growth Differentiation Factors, Mice, Phosphatidylinositol 3-Kinases, R5-920, Ischemia, Pregnancy, GDF11, Bone Morphogenetic Proteins, Animals, Female, Angiogenesis, Cells, Cultured
Abstract

Background The efficacy of stem cell therapy for ischemia repair has been limited by low cell retention rate. Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-β super family, which has multiple effects on development, physiology and diseases. The objective of the study is to investigate whether GDF11 could affect the efficacy of stem cell transplantation. Methods We explored the effects of GDF11 on proangiogenic activities of mesenchymal stem cells (MSCs) for angiogenic therapy in vitro and in vivo. Results Mouse bone marrow-derived MSCs were transduced with lentiviral vector to overexpress GDF11 (MSCGDF11). After exposed to hypoxia and serum deprivation for 48 h, MSCGDF11 were significantly better in viability than control MSCs (MSCvector). MSCGDF11 also had higher mobility and better angiogenic paracrine effects. The cytokine antibody array showed more angiogenic cytokines in the conditioned medium of MSCGDF11 than that of MSCvector, such as epidermal growth factor, platelet-derived growth factor-BB, placenta growth factor. When MSCs (1 × 106 cells in 50 μl) were injected into ischemic hindlimb of mice after femoral artery ligation, MSCGDF11 had higher retention rate in the muscle than control MSCs. Injection of MSCGDF11 resulted in better blood reperfusion and limb salvage than that of control MSCs after 14 days. Significantly more CD31+ endothelial cells and α-SMA + smooth muscle cells were detected in the ischemic muscles that received MSCGDF11. The effects of GDF11 were through activating TGF-β receptor and PI3K/Akt signaling pathway. Conclusion Our study demonstrated an essential role of GDF11 in promoting therapeutic functions of MSCs for ischemic diseases by enhancing MSC viability, mobility, and angiogenic paracrine functions. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02519-y.

Published
2021

34. A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5‐Mediated GDF6 Expression

Author

Wu, Rongrong, primary, Hu, Wangxing, additional, Chen, Huan, additional, Wang, Yingchao, additional, Li, Qingju, additional, Xiao, Changchen, additional, Fan, Lin, additional, Zhong, Zhiwei, additional, Chen, Xiaoying, additional, Lv, Kaiqi, additional, Zhong, Shuhan, additional, Shi, Yanna, additional, Chen, Jinghai, additional, Zhu, Wei, additional, Zhang, Jianyi, additional, Hu, Xinyang, additional, and Wang, Jian'an, additional

Published
2021
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40. Small extracellular vesicles containing miR-486-5p promote angiogenesis after myocardial infarction in mice and nonhuman primates

Author

Li, Qingju, primary, Xu, Yinchuan, additional, Lv, Kaiqi, additional, Wang, Yingchao, additional, Zhong, Zhiwei, additional, Xiao, Changchen, additional, Zhu, Keyang, additional, Ni, Cheng, additional, Wang, Kan, additional, Kong, Minjian, additional, Li, Xuebiao, additional, Fan, Youqi, additional, Zhang, Fengjiang, additional, Chen, Qi, additional, Li, Yi, additional, Li, Qian, additional, Liu, Chengjia, additional, Zhu, Jinyun, additional, Zhong, Shuhan, additional, Wang, Jingyi, additional, Chen, Yongjian, additional, Zhao, Jing, additional, Zhu, Dan, additional, Wu, Rongrong, additional, Chen, Jinghai, additional, Zhu, Wei, additional, Yu, Hong, additional, Ardehali, Reza, additional, Zhang, Jianyi(Jay), additional, Wang, Jian’an, additional, and Hu, Xinyang, additional

Published
2021
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