Transforming growth factor-Beta inhibits heme oxygenase-1 expression in lung fibroblast through nuclear factor-kappa-B-dependent pathway.
BACKGROUND
Heme oxygenase-1 (HO-1) contributes to the pathogenesis of pulmonary fibrosis. However, the expression of HO-1 in fibroblasts under fibrotic conditions has not been studied.


METHODS
This study was conducted to investigate the expression of HO-1 in lung fibroblasts from mice and humans under fibrotic conditions by Western blot.


RESULTS
We found that the expression of HO-1 was significantly decreased in lung fibroblasts isolated from bleomycin-challenged mice in comparison with control mice. Transforming growth factor-β (TGF-β) inhibited HO-1 expression and induced differentiation in human lung fibroblasts. Pretreatment with nuclear factor-κB (NF-κB) activation inhibitor or knockdown of the NF-κB p65 subunit attenuated TGF-β-induced inhibition of HO-1 expression and differentiation in human lung fibroblasts. Similarly, lysophosphatidic acid (LPA) induced TGF-β expression and decreased HO-1 expression in human lung fibroblasts. Interestingly, pretreatment with neutralized anti-TGF-β antibody attenuated LPA effects in human lung fibroblasts.


CONCLUSIONS
These data suggested that TGF-β inhibited HO-1 expression in human lung fibroblasts through activation of NF-κB.
Department of Anesthesiology, Huai'an Hospital Affiliated with Xuzhou Medical College and Huai'an Second People's Hospital, Huaian, China.
Ying
Y
Xie
Ye
Y
Wang
Chuanyue
C
Zong
Jiawen
J
Cheng
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000503:physiopathology*; D051996:Transcription Factor RelA / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D008246:Lysophospholipids; D016328:NF-kappa B; D051996:Transcription Factor RelA; D016212:Transforming Growth Factor beta; D051547:Heme Oxygenase-1; C032881:lysophosphatidic acid