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Phenylbutyrate decreases type I collagen production in human lung fibroblasts
Author(s) -
Rishikof David C.,
Ricupero Dennis A.,
Liu Hanqiao,
Goldstein Ronald H.
Publication year - 2004
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10742
Subject(s) - acetylation , transforming growth factor , extracellular matrix , type i collagen , chemistry , histone deacetylase , phenylbutyrate , microbiology and biotechnology , fibroblast , western blot , northern blot , histone , endocrinology , medicine , messenger rna , biology , biochemistry , in vitro , gene
Fibrotic lung diseases are characterized by excess extracellular matrix production, in particular type I collagen. Phenylbutyrate (PB) is a non‐toxic pharmacological compound that functions as a weak histone deacetylase inhibitor. In hepatic stellate cells, the synthesis of type I collagen expression is decreased by inhibiting histone acetylation. Our studies examined the regulation of type I collagen by PB in human lung fibroblasts. We found that PB decreases basal and transforming growth factor‐β‐stimulated α1(I) collagen mRNA and protein levels. Northern blot analyses demonstrated that PB decreases steady‐state α1(I) collagen mRNA levels by 78% without significantly changing the stability of the mRNA transcript. PB stimulates cAMP production and increases the acetylation of histone H4, but does not affect the activity of two transforming growth factor‐β (TGF‐β)‐responsive luciferase reporter constructs. These data suggest that PB regulates type I collagen expression in human lung fibroblasts by mechanisms that include cAMP production and histone acetylation. PB may have therapeutic use in fibrotic lung diseases. © 2004 Wiley‐Liss, Inc.