Evidence map›Paper›PMID 39571732›Full record

ArticleJournal of advanced research2025

miR-3606-3p alleviates skin fibrosis by integratively suppressing the integrin/FAK, p-AKT/p-ERK, and TGF-β signaling cascades.

Yahui Chen, Yiyi Gong, Mengkun Shi, Haoxing Zhu, Yulong Tang, Delin Huang, Wei Wang, Chenyi Shi, Xueyi Xia, Ying Zhang and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Yahui ChenDepartment of Dermatology, Huashan Hospital and Human Phenome Institute, Fudan University, Shanghai, China.
Yiyi GongDepartment of Dermatology, Huashan Hospital and Human Phenome Institute, Fudan University, Shanghai, China.
Mengkun ShiDepartment of Thoracic Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai, China.
Haoxing ZhuDepartment of Dermatology, Huashan Hospital and Human Phenome Institute, Fudan University, Shanghai, China.
Yulong TangState Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
Delin HuangState Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
Wei WangState Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
Chenyi ShiState Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
Xueyi XiaDepartment of Dermatology, Huashan Hospital and Human Phenome Institute, Fudan University, Shanghai, China.
Ying ZhangDepartment of Dermatology, Huashan Hospital and Human Phenome Institute, Fudan University, Shanghai, China.
Jianlan LiuDepartment of Dermatology, Huashan Hospital and Human Phenome Institute, Fudan University, Shanghai, China.
Jia HuangDepartment of Dermatology, Huashan Hospital and Human Phenome Institute, Fudan University, Shanghai, China.
Mengguo LiuDepartment of Dermatology, Huashan Hospital and Human Phenome Institute, Fudan University, Shanghai, China.
Huyan ChenDepartment of Dermatology, Huashan Hospital and Human Phenome Institute, Fudan University, Shanghai, China.
Yanyun MaState Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
Ziyu WangState Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
Lei WangDivision of Rheumatology, Shanghai TCM-Integrated Hospital, Shanghai, China.
Wenzhen TuDivision of Rheumatology, Shanghai TCM-Integrated Hospital, Shanghai, China.
Yinhuan ZhaoDivision of Rheumatology, Shanghai TCM-Integrated Hospital, Shanghai, China.
Jinran LinDepartment of Dermatology, Huashan Hospital and Human Phenome Institute, Fudan University, Shanghai, China.
Li JinState Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
Jörg Hw DistlerUniversity Hospital Düsseldorf and Heinrich-Heine University, Düsseldorf, Germany.
Wenyu WuDepartment of Dermatology, Huashan Hospital, Shanghai Institute of Dermatology, State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai, China; Department of Dermatology, Jing'an District Central Hospital, Shanghai, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, and Academy for Engineering and Technology, Fudan University, Shanghai, China. Electronic address: wuwenyu@huashan.org.cn.
Jiucun WangDepartment of Dermatology, Huashan Hospital and Human Phenome Institute, Fudan University, Shanghai, China; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China; Deptartment of Allergy and Immunology, Huashan Hospital, and Research Center of Allergy and Diseases, Fudan University, Shanghai, China; Research Unit of Dissecting the Population Genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058), Chinese Academy of Medical Sciences, Shanghai, China. Electronic address: jcwang@fudan.edu.cn.
Xiangguang ShiDepartment of Dermatology, Huashan Hospital and Human Phenome Institute, Fudan University, Shanghai, China. Electronic address: guangxiangshi@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionFibroblast abnormalities are crucial causes of skin fibrosis, including systemic sclerosis (SSc) and keloids. However, their mechanisms, including underlying microRNA regulatory mechanisms, remain elusive.

objectivesThis study aimed to evaluate the roles, mechanisms, and therapeutic potential of miR-3606-3p in regulating multiple fibroblast abnormalities.

methodsThe miR-3606-3p levels were evaluated in skin tissues and primary fibroblasts. RNA-seq and luciferase assays were employed to identify miR-3606-3p targets. Collagen contraction, western blotting, in vivo imaging, and real-time cellular analysis were used to assess fibroblast abnormalities. The therapeutic potential of miR-3606-3p was evaluated in mice.

resultsMiR-3606-3p decreased in skin tissues (SSc: Fold Change (FC) =  - 2.95, P = 0.0101; keloid: FC =  - 3.42, P < 0.0001) and primary fibroblasts (SSc: FC =  - 12.74, P = 0.0278; keloid: FC =  - 2.08, P = 0.0021) from skin fibrosis patients, and negatively correlated with disease severity. Mechanistically, miR-3606-3p targeted the 3'-untranslated regions (3'-UTRs) of Integrin αV (ITGAV), GRB2-associated binding protein 1 (GAB1), and transforming growth factor beta receptor 2 (TGFBR2), all of these three targets increased in skin fibrosis. Simultaneously, miR-3606-3p inhibited fibroblast's fibrogenesis, migration, inflammation, and proliferation by inhibiting ITGAV/integrin/FAK, GAB1/p-AKT/p-ERK, and TGFBR2/p-SMAD2/3 signaling. ITGAV-mediated integrin/FAK signaling unidirectionally activated the p-AKT/p-ERK and p-SMAD2/3 pathways. Knockdown of GAB1 and TGFRB2 reduced ITGAV-induced p-AKT/p-ERK and p-SMAD2/3 activities. MiR-3606-3p, si-ITGAV, si-GAB1, and si-TGFBR2 exhibited significant inhibition of fibrogenesis and migration. Inflammation was primarily inhibited by si-ITGAV and si-GAB1, while proliferation was primarily inhibited by si-TGFBR2. Moreover, miR-3606-3p significantly attenuates skin fibrosis in keloid-bearing mice.

conclusionsMiR-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.

Indexed as

KeloidMicroRNAsScleroderma, SystemicSkinAnimalsCell ProliferationCells, CulturedDisease Models, AnimalFibroblastsFibrosisFocal Adhesion Kinase 1HumansIntegrinsMaleMiceProto-Oncogene Proteins c-aktFocal Adhesion Kinase 1IntegrinsMicroRNAsProto-Oncogene Proteins c-aktTransforming Growth Factor betaFibroblast abnormalitiesGAB1ITGAVmiR-3606-3pSkin fibrosisTGFBR2

Identifiers

PMID39571732
PMCPMC12536609

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