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Updated: May 10, 2026
07:50
Immunohistochemical Detection of 5-Methylcytosine and 5-Hydroxymethylcytosine in Developing and Postmitotic Mouse Retina
Published on: August 29, 2018
m6A hypomethylation assembles a fibrogenic TCF7L2-Smad2/3 complex in pterygium
Xin Zhang1, Yue Li1, Xiaoyan Zhang2
1Department of Ophthalmology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, China.
Summary
Environmental factors drive pterygium progression by suppressing METTL3, which normally regulates fibrotic gene expression. This study reveals how epitranscriptomic changes impact TCF7L2-Smad2/3 complex formation, offering new therapeutic targets for fibrosis.
Area of Science:
- Ophthalmology
- Molecular Biology
- Epigenetics
Background:
- Pterygium progression involves conjunctival fibroblast fibrosis, influenced by TGF-β and Wnt signaling.
- The interplay between these pathways and epitranscriptomic regulation in pterygium is not well understood.
Purpose of the Study:
- To elucidate the epitranscriptomic mechanisms underlying pterygium fibrosis.
- To identify key molecular players and pathways involved in pterygium pathogenesis.
Main Methods:
- Investigated the role of METTL3 in human conjunctival fibroblasts under UV or inflammatory stimuli.
- Analyzed N6-methyladenosine (m6A) deposition on TCF7L2, Smad2, and Smad3 transcripts.
- Examined the formation of TCF7L2-Smad2/3 transcriptional complexes and their binding to target gene promoters (FN1, COL1A1).
- Modulated METTL3 expression in vitro and in vivo to assess effects on fibrotic phenotypes.
Main Results:
- UV or inflammatory stimuli suppressed METTL3 expression, reducing m6A on TCF7L2, Smad2, and Smad3 transcripts.
- METTL3 deficiency led to abnormal stabilization and accumulation of TCF7L2, Smad2, and Smad3 proteins.
- Elevated TCF7L2 formed a complex with Smad2/3, enhancing FN1 and COL1A1 expression and extracellular matrix deposition.
- METTL3 modulation reversed or mimicked TGF-β1-induced fibrotic phenotypes.
Conclusions:
- Environmental factors influence pterygium progression via epitranscriptomic regulation of fibrotic transcriptional complexes.
- METTL3-mediated m6A modification of TCF7L2, Smad2, and Smad3 is crucial for pterygium fibrosis.
- Targeting the epitranscriptome or specific transcriptional complexes presents potential therapeutic strategies for fibrosis.
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