TGFβ mediated transition of corneal fibroblasts from a proinflammatory state to a profibrotic state through modulation of histone acetylation

Qingjun Zhou, Lingling Yang, Yao Wang*, Mingli Qu, Peng Chen, Ye Wang*, Lixin Xie, Jing Zhao, Yiqiang Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Corneal fibroblasts exhibit different phenotypes in different phases of corneal wound healing. In the inflammatory phase, the cells assume a proinflammatory phenotype and produce large amounts of cytokines and chemokines, but in the proliferative and remodeling phases, they adapt a profibrotic state, differentiate into myofibroblasts and increase extracellular matrix protein synthesis, secretion, and deposition. In the present study, the molecular mechanisms regulating the transition of corneal fibroblasts from the proinflammatory state to the profibrotic state were investigated. Corneal fibroblasts were treated with TGFβ, a known profibrotic and anti-inflammatory factor in wound healing, in the absence or presence of trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor. The results revealed that TGFβ induced the profibrotic transition of corneal fibroblasts, including increased extracellular matrix synthesis, morphological changes, and assembly of actin filaments. Meanwhile, proinflammatory gene expressions of corneal fibroblasts were down-regulated with the treatment of TGFβ, as confirmed by cDNA microarray, real time PCR and ELISA. Moreover, TSA reversed the TGFβ-mediated transition of corneal fibroblasts from the proinflammatory state to the profibrotic state, as accompanied by histone hyperacetylations. In conclusion, TGFβ suppressed the production of proinflammatory factors and enhanced the expression of matrix remodeling genes of corneal fibroblasts in the transition from the proinflammatory state to the profibrotic state, and the dual roles of TGFβ on the phenotype regulations of corneal fibroblasts were mediated by altered histone acetylation.

Original languageEnglish
Pages (from-to)135-143
Number of pages9
JournalJournal of Cellular Physiology
Volume224
Issue number1
DOIs
Publication statusPublished - Jul 2010
Externally publishedYes

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