Open AccessMithramycin reduces expression of fibro‐proliferative mRNAs in human gingival fibroblasts
Author(s) -
Fajardo O. A.,
Thompson K.,
Parapuram S. K.,
Liu S.,
Leask A.
Publication year - 2011
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/j.1365-2184.2011.00738.x
Subject(s) - cell growth , fibroblast , extracellular matrix , microarray analysis techniques , transforming growth factor , growth factor , biology , ctgf , transforming growth factor beta , western blot , transcription factor , microbiology and biotechnology , cell culture , connective tissue , fibrosis , gene expression profiling , gene expression , cancer research , gene , pathology , medicine , biochemistry , genetics , receptor
Fibrosis is characterized by loss of normal structure and function of a tissue or organ resulting from excessive fibroblast proliferation and extracellular matrix production. Currently, there is no efficient treatment for fibrosis. Herein, we test effects of the drug mithramycin, which targets the Sp1 family of transcription factors, on mRNA expression by human gingival fibroblasts. Mithramycin reduced expression of connective tissue growth factor and type I collagen mRNAs. Microarray profiling revealed that mithramycin selectively blocked expression of cell proliferation and transforming growth factor‐beta (TGF‐β) signalling clusters. These microarray data were validated using real‐time polymerase chain reaction and western blot analyses. Mithramycin suppressed expression of key profibrotic TGF‐β signalling mediators, Smad3 and p300, as well as cell proliferation. Taken together, these data suggest that the Sp1 family of transcription factors may contribute to expression of fibrogenic genes in human gingival fibroblasts; drugs targeting the Sp1 family may be beneficial in treatment of fibro‐proliferative diseases.