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TGF-beta-induced interleukin-6 participates in transdifferentiation of human Tenon's fibroblasts to myofibroblasts

Authors
 Gong Je Seong  ;  Samin Hong  ;  Sun-Ah Jung  ;  Jung-Jin Lee  ;  Eunhae Lim  ;  Sung-Joo Kim  ;  Joon H. Lee 
Citation
 MOLECULAR VISION, Vol.15 : 2123-2128, 2009 
Journal Title
 MOLECULAR VISION 
Issue Date
2009
MeSH
Actins/metabolism ; Blotting, Western ; Cell Transdifferentiation/drug effects* ; Fibroblasts/cytology* ; Fibroblasts/drug effects* ; Fibroblasts/metabolism ; Fluorescent Antibody Technique ; Humans ; Interleukin-11/genetics ; Interleukin-11/metabolism ; Interleukin-6/genetics ; Interleukin-6/metabolism* ; Promoter Regions, Genetic/genetics ; RNA Interference/drug effects ; RNA, Small Interfering/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Deletion ; Transcription Factor AP-1/metabolism ; Transforming Growth Factor beta/pharmacology* ; Up-Regulation/drug effects
Abstract
PURPOSE: To gain a better understanding of the roles of interleukins (ILs) in subconjunctival fibrosis, we investigated their expression in transforming growth factor-beta1 (TGF-beta1)-stimulated Tenon's fibroblasts and examined their association with the transdifferentiation of fibroblasts to myofibroblasts. METHODS: After primary culture, fibroblasts derived from human Tenon's capsule were exposed to TGF-beta1. the expression of alpha-smooth muscle actin (alpha-SMA) protein was assessed by western immunoblots and immunofluorescence. the mRNA levels of various ILs were also evaluated by multiplex reverse transcription (RT)-PCR. Using the small interfering RNAs (siRNAs) specific for IL-6 and IL-11 and the promoter deletion assay, the contributions of IL-6 and IL-11 to TGF-beta1-induced induction of alpha-SMA were determined. RESULTS: in human Tenon's fibroblasts, TGF-beta1 stimulated the expression of alpha-SMA protein determined by western blot analysis and also increased the mRNA levels of IL-6 and IL-11 determined by multiplex RT-PCR. on the western immunoblots and immunofluorescence, the increased expression of alpha-SMA was attenuated only by the siRNAs specific for IL-6 but not by the siRNAs specific for IL-11. When the activator protein-1 binding sites of the IL-6 promoter region were deleted, the stimulation effects of TGF-beta1 decreased. CONCLUSIONS: Our data show that autocrine IL-6 may participate in the TGF-beta1-induced transdifferentiation of human Tenon's fibroblasts to myofibroblasts, which is known to be an essential step for subconjunctival fibrosis.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sung Joo(김성주)
Seong, Gong Je(성공제) ORCID logo https://orcid.org/0000-0002-5456-4296
Lee, Joon Haeng(이준행)
Hong, Sa Min(홍사민)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/105346
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