miR-3606-3p alleviates skin fibrosis by integratively suppressing the integrin/FAK, p-AKT/p-ERK, and TGF-β signaling cascades
MiR-3606-3p is downregulated in skin fibrosis. Moreover, it negatively correlates with disease severity. Functionally, miR-3606-3p inhibits fibrogenesis, migration, inflammation, and proliferation of fibroblasts. Mechanistically, miR-3606-3p inhibits ITGAV, GAB1, and TGFBR2 by targeting their 3'-UTRs. ITGAV-, GAB1-, and TGFBR2-activated integrin/AKT/ERK/SMAD2/3 signaling induced fibroblast abnormalities. In vivo, miR-3606-3p inhibits skin fibrosis in mice. Therefore, the multi-targeting, multi-phenotypic regulatory properties of miR-3606-3p suggest its potential utility in clinical treatment.
Authors
- Yulong Tang (ORCID: https://orcid.org/0000-0002-7794-2181)
- Yiyi Gong (ORCID: https://orcid.org/0000-0002-5400-9524)
- Jörg H. W. Distler (ORCID: https://orcid.org/0000-0001-7408-9333)
- Jian-Lan Liu (ORCID: https://orcid.org/0000-0003-0994-6401)
- Mengkun Shi
- Jiucun Wang (ORCID: https://orcid.org/0000-0003-2765-0620)
- Wenyu Wu (ORCID: https://orcid.org/0000-0002-7540-4953)
- Chenyi Shi
- Y Chen (ORCID: https://orcid.org/0009-0003-9797-429X)
- Mengguo Liu
- Ying Zhang (ORCID: https://orcid.org/0009-0000-4391-5516)
- Ziyu Wang (ORCID: https://orcid.org/0000-0001-6138-6566)
- Lei Wang (ORCID: https://orcid.org/0000-0002-7128-1896)
- Huyan Chen
- Jin Li (ORCID: https://orcid.org/0000-0001-6046-6935)
- Wei Wang (ORCID: https://orcid.org/0000-0003-3100-6184)
- Huimin Zhu (ORCID: https://orcid.org/0000-0002-4340-1125)
- Wenzhen Tu (ORCID: https://orcid.org/0000-0003-1541-5375)
- Xiangguang Shi (ORCID: https://orcid.org/0000-0002-3907-5822)
- Jinran Lin (ORCID: https://orcid.org/0000-0002-6816-9369)
- Yanyun Ma
- Xueyi Xia
- Jia Huang (ORCID: https://orcid.org/0000-0003-2493-6658)
- Yinhuan Zhao (ORCID: https://orcid.org/0000-0002-5991-761X)
- Delin Huang
Institutions
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Fudan University (CN)
- Düsseldorf University Hospital (DE)
- Integrated Chinese Medicine (China) (HK)
- Huashan Hospital (CN)
- State Key Laboratory of Genetic Engineering
- Heinrich Heine University Düsseldorf (DE)
Publication Details
- Journal
- Journal of Advanced Research
- Published
- 2024-11-19
- DOI
- https://doi.org/10.1016/j.jare.2024.11.027
- Citations
- 13
- Primary Topic
- Cell Adhesion Molecules Research
- Type
- article
- Field-Weighted Citation Impact
- 4.98
Funders
- National Science Foundation
- National Natural Science Foundation of China
- Shanghai Hospital Development Center
- Higher Education Discipline Innovation Project
- National Key Research and Development Program of China