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Indirect mitogenic effect of transforming growth factor-beta on cell proliferation of subconjunctival fibroblasts

Authors
 EunDuck P. Kay  ;  Hyung Keun Lee  ;  Kee Soon Park  ;  Sung Chul Lee 
Citation
 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol.39(3) : 481-486, 1998 
Journal Title
 INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 
ISSN
 0146-0404 
Issue Date
1998
MeSH
Animals ; Cell Count ; Cell Division/drug effects ; Cells, Cultured ; Conjunctiva/cytology ; Conjunctiva/drug effects* ; Conjunctiva/metabolism ; Culture Media, Conditioned ; DNA/biosynthesis ; DNA Replication ; Dose-Response Relationship, Drug ; Fibroblast Growth Factor 2/biosynthesis ; Fibroblast Growth Factor 2/genetics ; Fibroblasts/cytology ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Immunoblotting ; Mitogens/pharmacology* ; Oligonucleotides, Antisense/pharmacology ; Precipitin Tests ; Rabbits ; Transforming Growth Factor beta/biosynthesis ; Transforming Growth Factor beta/pharmacology*
Abstract
PURPOSE: To understand the mechanism of fibrosis after filtering surgery for glaucoma, the effect of transforming growth factor-beta (TGF-beta) was studied in subconjunctival fibroblasts (SCFs). TGF-beta, universal inhibitor of cell proliferation, stimulates the cell proliferation of fibroblasts. SCFs were evaluated for their production of TGF-beta and fibroblast growth factor 2 (FGF-2) to determine whether TGF-beta may be an indirect mitogen acting through the induction of an endogenous growth factor, or factors, that then acts as the direct mitogen in an autocrine manner. METHODS: Cell proliferation was determined either by counting cell numbers or by analyzing the incorporation of [3H]thymidine into DNA. The synthesis of TGF-beta and FGF-2 was analyzed by immunoprecipitation and immunoblotting. RESULTS: TGF-beta 1, TGF-beta 2, and TGF-beta 3 stimulated the cell proliferation of SCFs in a dose-dependent manner. The media conditioned by SCFs, which were subsequently activated by acid, stimulated cell proliferation of corneal stromal fibroblasts. When the acid-activated media conditioned by SCFs were immunoprecipitated, respectively, either with anti-TGF-beta 1 and TGF-beta 2 antibodies or with anti-TGF-beta 3 antibody, TGF-beta s, with an apparent molecular size of 25 kDa, were detected, whereas SCFs produced an 80-kDa latent form of TGF-beta 1. Interestingly, SCFs produced and secreted an 18-kDa extracellular isoform of FGF-2, the synthesis of which is further stimulated by TGF-beta 1 and TGF-beta 3, respectively, whereas the neutralizing antibody to FGF-2 and the FGF-2-specific antisense oligonucleotide primers inhibited the stimulatory activities of TGF-beta 1 in SCFs. CONCLUSIONS: These findings indicate that SCFs produce TGF-beta and FGF-2 and that FGF-2 seems to be the direct stimulator of TGF-beta-mediated cell proliferation in SCFs.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Hyung Keun(이형근) ORCID logo https://orcid.org/0000-0002-1123-2136
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/176889
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