Inducible Fgf13 ablation alleviates cardiac fibrosis via regulation of microtubule stability
Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, boasts significant potential for therapeutic intervention in cardiovascular dysfunctions. However, its impact on regulating fibrosis remains unexplored. This study aims to elucidate the role and mechanism of FGF13 on cardiac fibrosis...
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China Science Publishing & Media Ltd.
2024-05-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024075 |
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| author | Wang Cong Wang Xiangchong Zhang Yiyi Mi Yuan Han Yanxue Zhi Yaxin Zhao Ran Cui Nanqi Ma Qianli Zhang Huaxing Xue Dazhong Qiao Ruoyang Han Jiabing Yu Yulou Li Jiaxuan Shaiea Mohammed Liu Demin Gu Guoqiang Wang Chuan |
| author_facet | Wang Cong Wang Xiangchong Zhang Yiyi Mi Yuan Han Yanxue Zhi Yaxin Zhao Ran Cui Nanqi Ma Qianli Zhang Huaxing Xue Dazhong Qiao Ruoyang Han Jiabing Yu Yulou Li Jiaxuan Shaiea Mohammed Liu Demin Gu Guoqiang Wang Chuan |
| author_sort | Wang Cong |
| collection | DOAJ |
| description | Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, boasts significant potential for therapeutic intervention in cardiovascular dysfunctions. However, its impact on regulating fibrosis remains unexplored. This study aims to elucidate the role and mechanism of FGF13 on cardiac fibrosis. Here, we show that following transverse aortic constriction (TAC) surgery, interstitial fibrosis and collagen content increase in mice, along with reduced ejection fraction and fractional shortening, augmented heart mass. However, following Fgf13 deletion, interstitial fibrosis is decreased, ejection fraction and fractional shortening are increased, and heart mass is decreased, compared with those in the TAC group. Mechanistically, incubation of cardiac fibroblasts with transforming growth factor β (TGFβ) increases the expressions of types I and III collagen proteins, as well as α-smooth muscle actin (α-SMA) proteins, and enhances fibroblast proliferation and migration. In the absence of Fgf13, the expressions of these proteins are decreased, and fibroblast proliferation and migration are suppressed, compared with those in the TGFβ-stimulated group. Overexpression of FGF13, but not FGF13 mutants defective in microtubule binding and stabilization, rescues the decrease in collagen and α-SMA protein and weakens the proliferation and migration function of the Fgf13 knockdown group. Furthermore, Fgf13 knockdown decreases ROCK protein expression via microtubule disruption. Collectively, cardiac Fgf13 knockdown protects the heart from fibrosis in response to haemodynamic stress by modulating microtubule stabilization and ROCK signaling pathway. |
| format | Article |
| id | doaj-art-a4eb85917d4e4ebcb96a101cd926457a |
| institution | DOAJ |
| issn | 1672-9145 |
| language | English |
| publishDate | 2024-05-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-a4eb85917d4e4ebcb96a101cd926457a2025-08-20T02:46:43ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452024-05-01561802181210.3724/abbs.202407520d259ccInducible Fgf13 ablation alleviates cardiac fibrosis via regulation of microtubule stabilityWang Cong0Wang Xiangchong1Zhang Yiyi2Mi Yuan3Han Yanxue4Zhi Yaxin5Zhao Ran6Cui Nanqi7Ma Qianli8Zhang Huaxing9Xue Dazhong10Qiao Ruoyang11Han Jiabing12Yu Yulou13Li Jiaxuan14Shaiea Mohammed15Liu Demin16Gu Guoqiang17Wang Chuan18["Department of Pharmacology, the Key Laboratory of Neural and Vascular Biology, Ministry of Education, the Key Laboratory of New Drug Pharmacology and Toxicology, the Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Pharmacology, Hebei International Cooperation Center for Ion Channel Function and Innovative Traditional Chinese Medicine, Hebei Higher Education Institute Applied Technology Research Center on TCM Formula Preparation, Hebei University of Chinese Medicine, Shijiazhuang 050091, China"]["Department of Pharmacology, the Key Laboratory of Neural and Vascular Biology, Ministry of Education, the Key Laboratory of New Drug Pharmacology and Toxicology, the Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Emergency, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China"]["Department of Pharmacology, the Key Laboratory of Neural and Vascular Biology, Ministry of Education, the Key Laboratory of New Drug Pharmacology and Toxicology, the Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Cardiology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China"]["Department of Pharmacology, the Key Laboratory of Neural and Vascular Biology, Ministry of Education, the Key Laboratory of New Drug Pharmacology and Toxicology, the Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Vascular Surgery, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China"]["of Cardiac Surgery, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China"]["Core Facilities and Centers, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Pharmacology, the Key Laboratory of Neural and Vascular Biology, Ministry of Education, the Key Laboratory of New Drug Pharmacology and Toxicology, the Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang 050017, China"]["College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Pharmacology, the Key Laboratory of Neural and Vascular Biology, Ministry of Education, the Key Laboratory of New Drug Pharmacology and Toxicology, the Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Pharmacology, the Key Laboratory of Neural and Vascular Biology, Ministry of Education, the Key Laboratory of New Drug Pharmacology and Toxicology, the Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang 050017, China"]["School, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Pharmacology, the Key Laboratory of Neural and Vascular Biology, Ministry of Education, the Key Laboratory of New Drug Pharmacology and Toxicology, the Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang 050017, China"]["Department of Cardiology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China"]["Department of Cardiology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China"]["Department of Pharmacology, the Key Laboratory of Neural and Vascular Biology, Ministry of Education, the Key Laboratory of New Drug Pharmacology and Toxicology, the Hebei Collaboration Innovation Center for Mechanism, Diagnosis and Treatment of Neurological and Psychiatric Disease, Hebei Medical University, Shijiazhuang 050017, China"]Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, boasts significant potential for therapeutic intervention in cardiovascular dysfunctions. However, its impact on regulating fibrosis remains unexplored. This study aims to elucidate the role and mechanism of FGF13 on cardiac fibrosis. Here, we show that following transverse aortic constriction (TAC) surgery, interstitial fibrosis and collagen content increase in mice, along with reduced ejection fraction and fractional shortening, augmented heart mass. However, following Fgf13 deletion, interstitial fibrosis is decreased, ejection fraction and fractional shortening are increased, and heart mass is decreased, compared with those in the TAC group. Mechanistically, incubation of cardiac fibroblasts with transforming growth factor β (TGFβ) increases the expressions of types I and III collagen proteins, as well as α-smooth muscle actin (α-SMA) proteins, and enhances fibroblast proliferation and migration. In the absence of Fgf13, the expressions of these proteins are decreased, and fibroblast proliferation and migration are suppressed, compared with those in the TGFβ-stimulated group. Overexpression of FGF13, but not FGF13 mutants defective in microtubule binding and stabilization, rescues the decrease in collagen and α-SMA protein and weakens the proliferation and migration function of the Fgf13 knockdown group. Furthermore, Fgf13 knockdown decreases ROCK protein expression via microtubule disruption. Collectively, cardiac Fgf13 knockdown protects the heart from fibrosis in response to haemodynamic stress by modulating microtubule stabilization and ROCK signaling pathway.https://www.sciengine.com/doi/10.3724/abbs.2024075FGF13cardiac fibrosisfibroblastsmicrotubuleROCK |
| spellingShingle | Wang Cong Wang Xiangchong Zhang Yiyi Mi Yuan Han Yanxue Zhi Yaxin Zhao Ran Cui Nanqi Ma Qianli Zhang Huaxing Xue Dazhong Qiao Ruoyang Han Jiabing Yu Yulou Li Jiaxuan Shaiea Mohammed Liu Demin Gu Guoqiang Wang Chuan Inducible Fgf13 ablation alleviates cardiac fibrosis via regulation of microtubule stability Acta Biochimica et Biophysica Sinica FGF13 cardiac fibrosis fibroblasts microtubule ROCK |
| title | Inducible Fgf13 ablation alleviates cardiac fibrosis via regulation of microtubule stability |
| title_full | Inducible Fgf13 ablation alleviates cardiac fibrosis via regulation of microtubule stability |
| title_fullStr | Inducible Fgf13 ablation alleviates cardiac fibrosis via regulation of microtubule stability |
| title_full_unstemmed | Inducible Fgf13 ablation alleviates cardiac fibrosis via regulation of microtubule stability |
| title_short | Inducible Fgf13 ablation alleviates cardiac fibrosis via regulation of microtubule stability |
| title_sort | inducible fgf13 ablation alleviates cardiac fibrosis via regulation of microtubule stability |
| topic | FGF13 cardiac fibrosis fibroblasts microtubule ROCK |
| url | https://www.sciengine.com/doi/10.3724/abbs.2024075 |
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