Burn injury induces an inhibitory signal in the lung Smad pathway

Tam N. Pham, Kiho Cho, Lee K. Adamson, Milad Hakimbashi, Liju Yang, Edward E. Tredget, David G Greenhalgh

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Smad signaling mediates the cellular response to transforming growth factor-β (TGF-β). We hypothesize that variations in Smad signaling modify the response to TGF-β signaling in the lung after injury. C57BLKS/J mice were subjected to an 18% surface area burn injury, sacrificed at specific time points and their lung tissue was harvested. Lung TGF-β1 expression, as determined by RT-PCR, ELISA and PAI/Luciferase assay, was not affected by injury. Western blots for Smad2/3 and Smad4 on nuclear fractions revealed decreased Smad2, Smad3, and Smad4 protein levels at 3h, while their total cellular levels did not differ from control mice. Smad7 protein increased transiently at 3h. Correlating with Smad inhibition, transcription in type I alpha-2 collagen was also transiently depressed. By RT-PCR, Smad3 and Smad7 mRNAs decreased at 3h, while Smad2 and Smad4 mRNA levels remained constitutive. Burn injury did not alter lung TGF-β1 expression but caused Smad inhibition through decreased nuclear translocation of Smad2, Smad3, and Smad4, and upregulated Smad7. Transcription was not the key regulatory step in Smad protein expression, as transient decreases in Smad3 and Smad7 mRNA did not correlate with protein levels. It appears that Smad activity may in part attenuate TGF-β activity after burn injury.

Original languageEnglish (US)
Pages (from-to)66-73
Number of pages8
JournalCytokine
Volume27
Issue number2-3
DOIs
StatePublished - Jul 21 2004

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Keywords

  • Mice
  • Nucleus
  • Systemic response
  • TGF-β
  • Transcription

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy

Cite this

Pham, T. N., Cho, K., Adamson, L. K., Hakimbashi, M., Yang, L., Tredget, E. E., & Greenhalgh, D. G. (2004). Burn injury induces an inhibitory signal in the lung Smad pathway. Cytokine, 27(2-3), 66-73. https://doi.org/10.1016/j.cyto.2004.03.015