Retinoic acid inhibition of transforming growth factor-beta-induced collagen production by human lung fibroblasts

Am J Respir Cell Mol Biol. 1995 Mar;12(3):287-95. doi: 10.1165/ajrcmb.12.3.7873195.


Transforming growth factor-beta (TGF-beta)-stimulated collagen production plays an important role in the pathogenesis of the fibrotic response seen in chronic inflammatory lung disorders. Retinoids are vitamin A analogues that are potent immunomodulators and have been shown to modulate stromal cell collagen production in a variety of nonpulmonary systems. We hypothesized that retinoids might also modulate lung fibroblast collagen production. To test this hypothesis, we determined whether all-trans retinoic acid (RA) and several other retinoid compounds regulate the production of types I and III collagen by unstimulated and TGF-beta 1-stimulated human lung fibroblasts. Unstimulated cells produced modest quantities of types I and III collagen, and TGF-beta 1 increased the production of these matrix molecules 2- to 4-fold. Preincubation with 10(-5) M RA caused a significant decrease in the basal levels of types I and III collagen produced by these cells. RA preincubation also totally abrogated the collagen inductive effects of TGF-beta 1. At 10(-5) M, RA preincubation caused a 97% decrease in the stimulation of type I collagen and a 115% decrease in the stimulation of type III collagen caused by TGF-beta 1. These inhibitory effects were dose dependent. Significant inhibition of type I and III collagen production was appreciated with doses of RA as low as 10(-9) and 10(-8), respectively. These inhibitory effects were not unique to RA since 13-cis-retinoic acid, 9-cis-retinoic acid, etretinate, all-trans etretin, and the water-soluble retinoids, retinoyl beta-glucuronide and retinyl-beta-glucuronide, also inhibited TGF-beta 1-stimulated type I collagen production.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line
  • Cells, Cultured
  • Collagen / biosynthesis*
  • Fibroblasts / metabolism
  • Gene Expression / drug effects
  • Humans
  • In Vitro Techniques
  • Interleukin-11 / genetics
  • Lung / cytology
  • Lung / metabolism*
  • RNA, Messenger / genetics
  • Transcription, Genetic / drug effects
  • Transforming Growth Factor beta / pharmacology*
  • Tretinoin / pharmacology*


  • Interleukin-11
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Tretinoin
  • Collagen