JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target
Cardiac fibrosis is a serious health problem because it is a common pathological change in almost all forms of cardiovascular diseases. Cardiac fibrosis is characterized by the transdifferentiation of cardiac fibroblasts (CFs) into cardiac myofibroblasts and the excessive deposition of extracellular...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-03-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1336102/full |
| _version_ | 1797289760169918464 |
|---|---|
| author | Heng Jiang Junjie Yang Tao Li Xinyu Wang Zhongcai Fan Qiang Ye Yanfei Du Yanfei Du |
| author_facet | Heng Jiang Junjie Yang Tao Li Xinyu Wang Zhongcai Fan Qiang Ye Yanfei Du Yanfei Du |
| author_sort | Heng Jiang |
| collection | DOAJ |
| description | Cardiac fibrosis is a serious health problem because it is a common pathological change in almost all forms of cardiovascular diseases. Cardiac fibrosis is characterized by the transdifferentiation of cardiac fibroblasts (CFs) into cardiac myofibroblasts and the excessive deposition of extracellular matrix (ECM) components produced by activated myofibroblasts, which leads to fibrotic scar formation and subsequent cardiac dysfunction. However, there are currently few effective therapeutic strategies protecting against fibrogenesis. This lack is largely because the molecular mechanisms of cardiac fibrosis remain unclear despite extensive research. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling cascade is an extensively present intracellular signal transduction pathway and can regulate a wide range of biological processes, including cell proliferation, migration, differentiation, apoptosis, and immune response. Various upstream mediators such as cytokines, growth factors and hormones can initiate signal transmission via this pathway and play corresponding regulatory roles. STAT3 is a crucial player of the JAK/STAT pathway and its activation is related to inflammation, malignant tumors and autoimmune illnesses. Recently, the JAK/STAT3 signaling has been in the spotlight for its role in the occurrence and development of cardiac fibrosis and its activation can promote the proliferation and activation of CFs and the production of ECM proteins, thus leading to cardiac fibrosis. In this manuscript, we discuss the structure, transactivation and regulation of the JAK/STAT3 signaling pathway and review recent progress on the role of this pathway in cardiac fibrosis. Moreover, we summarize the current challenges and opportunities of targeting the JAK/STAT3 signaling for the treatment of fibrosis. In summary, the information presented in this article is critical for comprehending the role of the JAK/STAT3 pathway in cardiac fibrosis, and will also contribute to future research aimed at the development of effective anti-fibrotic therapeutic strategies targeting the JAK/STAT3 signaling. |
| first_indexed | 2024-03-07T19:10:37Z |
| format | Article |
| id | doaj.art-a9dde22c0ea04995976f2b6e3bf2ce9d |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-07T19:10:37Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-a9dde22c0ea04995976f2b6e3bf2ce9d2024-03-01T04:54:54ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-03-011510.3389/fphar.2024.13361021336102JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic targetHeng Jiang0Junjie Yang1Tao Li2Xinyu Wang3Zhongcai Fan4Qiang Ye5Yanfei Du6Yanfei Du7Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, ChinaDepartment of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, ChinaCardiac fibrosis is a serious health problem because it is a common pathological change in almost all forms of cardiovascular diseases. Cardiac fibrosis is characterized by the transdifferentiation of cardiac fibroblasts (CFs) into cardiac myofibroblasts and the excessive deposition of extracellular matrix (ECM) components produced by activated myofibroblasts, which leads to fibrotic scar formation and subsequent cardiac dysfunction. However, there are currently few effective therapeutic strategies protecting against fibrogenesis. This lack is largely because the molecular mechanisms of cardiac fibrosis remain unclear despite extensive research. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling cascade is an extensively present intracellular signal transduction pathway and can regulate a wide range of biological processes, including cell proliferation, migration, differentiation, apoptosis, and immune response. Various upstream mediators such as cytokines, growth factors and hormones can initiate signal transmission via this pathway and play corresponding regulatory roles. STAT3 is a crucial player of the JAK/STAT pathway and its activation is related to inflammation, malignant tumors and autoimmune illnesses. Recently, the JAK/STAT3 signaling has been in the spotlight for its role in the occurrence and development of cardiac fibrosis and its activation can promote the proliferation and activation of CFs and the production of ECM proteins, thus leading to cardiac fibrosis. In this manuscript, we discuss the structure, transactivation and regulation of the JAK/STAT3 signaling pathway and review recent progress on the role of this pathway in cardiac fibrosis. Moreover, we summarize the current challenges and opportunities of targeting the JAK/STAT3 signaling for the treatment of fibrosis. In summary, the information presented in this article is critical for comprehending the role of the JAK/STAT3 pathway in cardiac fibrosis, and will also contribute to future research aimed at the development of effective anti-fibrotic therapeutic strategies targeting the JAK/STAT3 signaling.https://www.frontiersin.org/articles/10.3389/fphar.2024.1336102/fullcardiovascular diseasesJAK/STAT3 signalingcardiac fibrosiscardiac fibroblast proliferation and activationsignal transduction and regulationupstream mediators |
| spellingShingle | Heng Jiang Junjie Yang Tao Li Xinyu Wang Zhongcai Fan Qiang Ye Yanfei Du Yanfei Du JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target Frontiers in Pharmacology cardiovascular diseases JAK/STAT3 signaling cardiac fibrosis cardiac fibroblast proliferation and activation signal transduction and regulation upstream mediators |
| title | JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target |
| title_full | JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target |
| title_fullStr | JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target |
| title_full_unstemmed | JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target |
| title_short | JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target |
| title_sort | jak stat3 signaling in cardiac fibrosis a promising therapeutic target |
| topic | cardiovascular diseases JAK/STAT3 signaling cardiac fibrosis cardiac fibroblast proliferation and activation signal transduction and regulation upstream mediators |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1336102/full |
| work_keys_str_mv | AT hengjiang jakstat3signalingincardiacfibrosisapromisingtherapeutictarget AT junjieyang jakstat3signalingincardiacfibrosisapromisingtherapeutictarget AT taoli jakstat3signalingincardiacfibrosisapromisingtherapeutictarget AT xinyuwang jakstat3signalingincardiacfibrosisapromisingtherapeutictarget AT zhongcaifan jakstat3signalingincardiacfibrosisapromisingtherapeutictarget AT qiangye jakstat3signalingincardiacfibrosisapromisingtherapeutictarget AT yanfeidu jakstat3signalingincardiacfibrosisapromisingtherapeutictarget AT yanfeidu jakstat3signalingincardiacfibrosisapromisingtherapeutictarget |