Burn injury induces an inhibitory signal in the lung Smad pathway.
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 appears that Smad activity may in part attenuate TGF-beta activity after burn injury.
Pham
Tam N
TN
Burn Surgery, Shriners Hospitals for Children Northern California, and Department of Surgery, University of California at Davis, Sacramento, CA 95817, USA.
Cho
Kiho
K
Adamson
Lee K
LK
Hakimbashi
Milad
M
Yang
Liju
L
Tredget
Edward E
EE
Greenhalgh
David G
DG
D000818:Animals; D002056:Burns / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D051785:Smad Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D051785:Smad Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta