ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Translational Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1623640
This article is part of the Research TopicImmunological Aspects of Fibrosis Pathogenesis: Novel Mechanisms and Therapeutic StrategiesView all 26 articles
Locked Nucleic Acid-Modified Antisense Oligonucleotides Attenuate Scar Hyperplasia through Targeted Inhibition of CTGF
Provisionally accepted
Jinhe Li1
Xi Wu1Ying Yang1Ruiqi Mao1Zherui Li1Xiujun Zhang2Wenguo Wei3Wendi Wang4*Hailong Li1*
Honggang Zhou1*
Cheng Yang1*- 1Nankai University, Tianjin, China
- 2Department of Dermatology, Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, tianjin, China
- 3Department of Dermatology，Tianjin First Central Hospital，School of Medicine, tianjin, China
- 4Department of Plastic and Burn Surgery, Tianjin First Central Hospital, No.24 Kangfu Road, Nankai District,, tianjin, China
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Connective tissue growth factor (CTGF) is notably upregulated in scar tissue, making it a promising target for therapeutic intervention. Here, we have designed and screened an antisense oligonucleotide (ASO)that binds specifically to the exon 5 sequence of CTGF, with particular emphasis on the use of 2'-O-methoxyethyl (MOE) and locked nucleic acid (LNA) modifications to enhance stability and specificity.In vitro experiments demonstrated that both MOE-ASO#1 and LNA-ASO#1 significantly inhibited fibroblast proliferation and extracellular matrix protein expression. In vivo studies using mouse and rabbit scar models, as well as a nude mouse keloid xenograft model, revealed that these ASOs effectively reduced scar formation and keloid growth while also suppressing IL-6 expression. LNA-ASO#1 showed superior pharmacodynamics compared to MOE-ASO#1. Mechanistic investigations indicated that the ASOs exert their antifibrotic effects by inhibiting the TGF-β1 pathway, myofibroblast activation, and extracellular matrix production. These findings suggest that LNA-ASO#1 is a promising therapeutic strategy for the treatment of scars.
Keywords: ctgf, Antisense oligonucleotide, SCAR, LNA, Fibrosis
Received: 06 May 2025; Accepted: 12 Aug 2025.
Copyright: © 2025 Li, Wu, Yang, Mao, Li, Zhang, Wei, Wang, Li, Zhou and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Wendi Wang, Department of Plastic and Burn Surgery, Tianjin First Central Hospital, No.24 Kangfu Road, Nankai District,, tianjin, China
Hailong Li, Nankai University, Tianjin, China
Honggang Zhou, Nankai University, Tianjin, China
Cheng Yang, Nankai University, Tianjin, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.