2. Academic Validation
  3. MicroRNA-21a-5p inhibition alleviates systemic sclerosis by targeting STAT3 signaling

MicroRNA-21a-5p inhibition alleviates systemic sclerosis by targeting STAT3 signaling

  • J Transl Med. 2024 Apr 1;22(1):323. doi: 10.1186/s12967-024-05056-3.
Jin-Sil Park 1 2,  Chongtae Kim 3,  JeongWon Choi 1 2,  Ha Yeon Jeong 1 2,  Young-Mee Moon 1,  Hoin Kang 3,  Eun Kyung Lee # 4,  Mi-La Cho # 5 6 7 8,  Sung-Hwan Park # 9 10
Affiliations

Affiliations

  • 1 The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, South Korea.
  • 2 Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, South Korea.
  • 3 Department of Biochemistry, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, South Korea.
  • 4 Department of Biochemistry, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, South Korea. leeek@catholic.ac.kr.
  • 5 The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, South Korea. iammila@catholic.ac.kr.
  • 6 Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, Seoul, South Korea. iammila@catholic.ac.kr.
  • 7 Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, South Korea. iammila@catholic.ac.kr.
  • 8 Lab of Translational ImmunoMedicine, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, South Korea. iammila@catholic.ac.kr.
  • 9 The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, South Korea. rapark@catholic.ac.kr.
  • 10 Divison of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-Daero, Seocho-Gu, Seoul, 06591, South Korea. rapark@catholic.ac.kr.
  • # Contributed equally.
PMID: 38561750 DOI: 10.1186/s12967-024-05056-3
Abstract

Background: MicroRNA (miRNA)-21-5p participates in various biological processes, including Cancer and autoimmune diseases. However, its role in the development of fibrosis in the in vivo model of systemic sclerosis (SSc) has not been reported. This study investigated the effects of miRNA-21a-5p overexpression and inhibition on SSc fibrosis using a bleomycin-induced SSc mouse model.

Methods: A murine SSc model was induced by subcutaneously injecting 100 μg bleomycin dissolved in 0.9% NaCl into C57BL/6 mice daily for 5 weeks. On days 14, 21, and 28 from the start of bleomycin injection, 100 μg pre-miRNA-21a-5p or anti-miRNA-21a-5p in 1 mL saline was hydrodynamically injected into the mice. Fibrosis analysis was conducted in lung and skin tissues of SSc mice using hematoxylin and eosin as well as Masson's trichrome staining. Immunohistochemistry was used to examine the expression of inflammatory cytokines, phosphorylated signal transducer and activator of transcription-3 (STAT3) at Y705 or S727, and Phosphatase and tensin homologue deleted on chromosome-10 (PTEN) in skin tissues of SSc mice.

Results: MiRNA-21a-5p overexpression promoted lung fibrosis in bleomycin-induced SSc mice, inducing infiltration of cells expressing TNF-α, IL-1β, IL-6, or IL-17, along with STAT3 phosphorylated cells in the lesional skin. Conversely, anti-miRNA-21a-5p injection improved fibrosis in the lung and skin tissues of SSc mice, reducing the infiltration of cells secreting inflammatory cytokines in the skin tissue. In particular, it decreased STAT3-phosphorylated cell infiltration at Y705 and increased the infiltration of PTEN-expressing cells in the skin tissue of SSc mice.

Conclusion: MiRNA-21a-5p promotes fibrosis in an in vivo murine SSc model, suggesting that its inhibition may be a therapeutic strategy for improving fibrosis in SSc.

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