Glutamine increases collagen gene transcription in cultured human fibroblasts

Biochim Biophys Acta. 1995 Sep 21;1268(3):311-23. doi: 10.1016/0167-4889(95)00093-8.


We have previously shown that glutamine stimulates the synthesis of collagen in human dermal confluent fibroblast cultures (Bellon, G. et al. [1987] Biochim. Biophys. Acta, 930, 39-47). In this paper, we examine the effects of glutamine on collagen gene expression. A dose-dependent effect of glutamine on collagen synthesis was demonstrated from 0 to 0.25 mM followed by a plateau up to 10 mM glutamine. Depending on the cell population, collagen synthesis was increased by 1.3-to 2.3-fold. The mean increase in collagen and non-collagen protein synthesis was 63% and 18% respectively. Steady-state levels of alpha 1(I) and alpha 1(III) mRNAs, were measured by hybridizing total RNA to specific cDNA probes at high stringency. Glutamine increased the steady-state level of collagen alpha 1(I) and alpha 1(III) mRNAs in a dose-dependent manner. At 0.15 mM glutamine, collagen mRNAs were increased by 1.7-and 2.3-fold respectively. Nuclear run-off experiments at this concentration of glutamine indicated that the transcriptional activity was increased by 3.4-fold for the pro alpha 1(I) collagen gene. The effect of glutamine on gene transcription was also supported by the measurement of pro alpha 1(I) collagen mRNA half-life since glutamine did not affect its stability. Protein synthesis seemed to be required for the glutamine-dependent induction of collagen gene expression since cycloheximide suppressed the activation. The effect of glutamine appeared specific because analogues and/or derivatives of glutamine, such as acivicin, 6-diazo-5-oxo-L-norleucine, homoglutamine, ammonium chloride and glutamate did not replace glutamine. The influence of amino acid transport systems through plasma membrane was assessed by the use of 2(methylamino)-isobutyric acid and beta 2-aminobicyclo-(2.2.1)-heptane-2-carboxylic acid. The glutamine-dependent induction of collagen gene expression was found to be independent of transport system A but dependent on transport system L whose inhibition induced a decrease in pro alpha 1(I) collagen gene transcription by an unknown mechanism. Thus, glutamine, at physiological concentrations, indirectly regulates collagen gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / pharmacology
  • Amino Acids, Cyclic*
  • Biological Transport / drug effects
  • Cells, Cultured / drug effects
  • Cells, Cultured / metabolism
  • Collagen / biosynthesis*
  • Collagen / genetics*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects*
  • Glutamine / analogs & derivatives
  • Glutamine / pharmacology*
  • Humans
  • Protein Biosynthesis
  • RNA, Messenger / analysis
  • Transcription, Genetic / drug effects*


  • Amino Acids
  • Amino Acids, Cyclic
  • RNA, Messenger
  • Glutamine
  • 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid
  • Collagen