Transforming Growth Factor-β1-induced Human Subconjunctival Fibrosis is Mediated by MicroRNA 143/145 Expression.

Abstract:

Purpose:To investigate the roles and pathways of microRNAs 143 and 145 in transforming growth factor (TGF)-β1-induced human subconjunctival fibrosis. Methods:Human tenon's capsule fibroblasts (HTFs) were obtained from a healthy eye. After treating cultured HTFs with TGF-β1, the expression of microRNAs 143 and 145 was evaluated using polymerase chain reaction. To identify the pathways of TGF-β1-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-β1-induced myofibroblast transdifferentiation, microRNA 143/145 mimics and microRNA 143/145 inhibitors were applied to the HTFs. Results:Array analysis revealed that TGF-β1 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-β1-induced expression of microRNA 143/145 was inhibited; however, SMAD2 and SMAD4 inhibition did not affect the TGF-β1-induced expression of these microRNAs. In the mutagenesis studies, both the CArG box and SBE were associated with TGF-β1-induced expression of microRNA 143/145. Mimics of microRNA 143/145 induced increased myofibroblast formation, whereas their inhibitors had the opposite effect. Conclusions:TGF-β1-induced human subconjunctival fibrosis was mediated by the expression of microRNA 143/145, mainly via SMAD-independent pathways. Inhibition of TGF-β1-induced microRNA 143/145 expression in HTFs might represent a novel strategy to prevent subconjunctival fibrosis.

authors

Hwang YH,Jung SA,Lyu J,Kim YY,Lee JH

doi

10.1167/iovs.19-26797

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

2064-2071

issue

6

eissn

0146-0404

issn

1552-5783

pii

2733666

journal_volume

60

pub_type

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