Abstract
Smad signaling mediates the cellular response to transforming growth factor-beta (TGF-beta). We hypothesize that variations in Smad signaling modify the response to TGF-beta 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-beta1 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 3 h. Correlating with Smad inhibition, transcription in type I alpha-2 collagen was also transiently depressed. By RT-PCR, Smad3 and Smad7 mRNAs decreased at 3 h, while Smad2 and Smad4 mRNA levels remained constitutive. Burn injury did not alter lung TGF-beta1 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 appea...Continue Reading
References
Oct 22, 1992·Nature·M M ShullD Calvin
Oct 1, 1991·The Journal of Clinical Investigation·M S Sawdey, D J Loskutoff
Mar 1, 1995·Genetics·J J SekelskyW M Gelbart
Sep 1, 1994·American Journal of Respiratory Cell and Molecular Biology·R ShenkarE Abraham
Feb 1, 1994·American Journal of Respiratory Cell and Molecular Biology·Z XingJ Gauldie
Mar 1, 1994·American Journal of Respiratory Cell and Molecular Biology·R ShenkarE Abraham
Jun 3, 1993·The New England Journal of Medicine·M S AnscherR L Jirtle
Aug 1, 1996·Shock·Y H KangC H Lee
Mar 17, 1997·Biochemical and Biophysical Research Communications·I Mucsi, H J Goldberg
Oct 23, 1997·Nature·A NakaoP ten Dijke
Aug 14, 1998·Molecular Cell·E LabbéL Attisano
Oct 31, 1998·Oncogene·K YanagisawaT Takahashi
Jan 23, 1999·The American Journal of Pathology·L YangG Brunner
May 26, 1999·Current Topics in Pathology. Ergebnisse Der Pathologie·J GauldieG M Tremblay
Jul 7, 1999·The Journal of Clinical Investigation·A NakaoI Iwamoto
Nov 13, 1999·Nature Cell Biology·G S AshcroftA B Roberts
Feb 2, 2000·Intensive Care Medicine·D R DanceyT E Stewart
Feb 7, 2001·The Journal of Biological Chemistry·G von GersdorffE P Böttinger
May 8, 2000·Journal of Cellular Physiology·S J ChenJ Varga
Jun 14, 2000·The Journal of Biological Chemistry·G BrodinR Heuchel
Sep 21, 2000·Kidney International. Supplement·M SchifferE P Böttinger
Mar 10, 2001·Shock·M A ChoudhryM M Sayeed
Jun 20, 2001·The Journal of Clinical Investigation·J F PittetD Sheppard
Jul 27, 2001·American Journal of Respiratory Cell and Molecular Biology·A RosendahlP Sideras
Nov 9, 2001·Shock·M VarediR E Barrow
Feb 13, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jingsong ZhaoDavid Warburton
Jun 19, 2002·The Journal of Surgical Research·Kristina G HobsonDavid G Greenhalgh
Citations
Sep 15, 2007·Critical Care Medicine·Kyros IpaktchiSaman Arbabi
May 23, 2008·Shock·Junping WangYongping Su
Apr 8, 2009·Journal of Burn Care & Research : Official Publication of the American Burn Association·Vincent Ashley Gabriel
Jun 2, 2007·European Journal of Pharmacology·Tian TangGuang Shan
Mar 3, 2012·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Keijiro HoriEdward E Tredget
Jan 18, 2006·Biochemical and Biophysical Research Communications·Zengli Yu, Ying Xing