Transforming Growth Factor-beta 1-induced Human Subconjunctival Fibrosis is Mediated by MicroRNA 143/145 Expression
- Authors
- Hwang, Young Hoon; Jung, Sun-Ah; Lyu, Jungmook; Kim, Yong Yeon; Lee, Joon H.
- Issue Date
- 5월-2019
- Publisher
- ASSOC RESEARCH VISION OPHTHALMOLOGY INC
- Keywords
- glaucoma; fibrosis; TGF-beta; microRNA; conjunctiva
- Citation
- INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v.60, no.6, pp.2064 - 2071
- Indexed
- SCIE
SCOPUS
- Journal Title
- INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
- Volume
- 60
- Number
- 6
- Start Page
- 2064
- End Page
- 2071
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/65927
- DOI
- 10.1167/iovs.19-26797
- ISSN
- 0146-0404
- Abstract
- PURPOSE. To investigate the roles and pathways of microRNAs 143 and 145 in transforming growth factor (TGF)-beta 1-induced human subconjunctival fibrosis. METHODS. Human tenon's capsule fibroblasts (HTFs) were obtained from a healthy eye. After treating cultured HTFs with TGF-beta 1, the expression of microRNAs 143 and 145 was evaluated using polymerase chain reaction. To identify the pathways of TGF-beta 1-induced microRNA 143/145 expression, HTFs were treated with specific inhibitors of p38MAPK, PI3K/Akt, JNK, ERK, and with siRNAs for SMAD2 and SMAD4. Mutagenesis studies were performed to evaluate the role of the CArG box and SMAD-binding element (SBE). To investigate the role of microRNA 143/145 in TGF-beta 1-induced myofibroblast transdifferentiation, microRNA 143/145 mimics and microRNA 143/145 inhibitors were applied to the HTFs. RESULTS. Array analysis revealed that TGF-beta 1 induced the expression of microRNA 143/145 in a dose-and time-dependent manner. When inhibitors and siRNAs for p38MAPK, PI3K/Akt, ERK, and JNK were applied, the TGF-beta 1-induced expression of microRNA 143/145 was inhibited; however, SMAD2 and SMAD4 inhibition did not affect the TGF-beta 1-induced expression of these microRNAs. In the mutagenesis studies, both the CArG box and SBE were associated with TGF-b1-induced expression of microRNA 143/145. Mimics of microRNA 143/145 induced increased myofibroblast formation, whereas their inhibitors had the opposite effect. CONCLUSIONS. TGF-beta 1-induced human subconjunctival fibrosis was mediated by the expression of microRNA 143/145, mainly via SMAD-independent pathways. Inhibition of TGF-beta 1-induced microRNA 143/145 expression in HTFs might represent a novel strategy to prevent subconjunctival fibrosis.
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