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Effect of IFN-gamma and dexamethasone on TGF-beta1-induced human fetal lung fibroblast-myofibroblast differentiation.
Acta Pharmacol Sin. 2004 Nov; 25(11):1479-88.AP

Abstract

AIM

To study whether Smads signaling pathway was involved in human fetal lung fibroblast-myofibroblast differentiation induced by transforming growth factor (TGF)-beta1 and the role of interferon (IFN)-gamma, dexamethasone (DEX) in the fibroblast-myofibroblast differentiation.

METHODS

Alpha-smooth muscle actin (alpha-SMA), Smad2/3, and Smad7 protein were assessed by Western blot. Collagen protein was analyzed by measuring hydroxyproline. Alpha-SMA and collagen III mRNA were assessed by RT-PCR. Myofibroblasts morphology and Smad2/3 nuclear translocation were assessed by immunohistochemistry. The overexpression of Smad7, a negative mediator of Smads signaling pathway, was acquired by transfection of Smad7 vector.

RESULTS

During fibroblast-myofibroblast differentiation induced by TGF-beta1, IFN-gamma 200 microg/L markedly blocked TGF-beta1-induced alpha-SMA protein expression (P<0.01), collagen protein (P<0.01) and mRNA (P<0.05) expression, and myofibroblasts morphological transformation, but DEX 10 micromol/L augmented TGF-beta1-induced alpha-SMA expression (P<0.01). For myofibroblasts, both IFN-gamma 200 microg/L and DEX 10 micromol/L did not inhibit alpha-SMA expression (P>0.05) and collagen protein (P>0.05) and mRNA expression (P>0.05) and did not change myofibroblasts morphology. Transient transfection of Smad7 vector resulted in significant inhibition of TGF-beta1-induced alpha-SMA expression (P<0.01). IFN-gamma 200 microg/L did not block TGF-beta1-stimulated Smad2/3 phosphorylation and their nuclear translocation.

CONCLUSION

TGF-beta1 induced fibroblast-myofibroblast differentiation in a Smad proteins-dependent manner. IFN-gamma could block this process but it was not mediated by interrupting smad2/3 phosphorylation and their nuclear translocation and DEX played a synergism with TGF-beta1. Differentiated myofibroblasts, however, were resistant to both IFN-gamma and DEX.

Authors+Show Affiliations

Department of Pulmonary Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15525471

Citation

Gu, Li, et al. "Effect of IFN-gamma and Dexamethasone On TGF-beta1-induced Human Fetal Lung Fibroblast-myofibroblast Differentiation." Acta Pharmacologica Sinica, vol. 25, no. 11, 2004, pp. 1479-88.
Gu L, Zhu YJ, Guo ZJ, et al. Effect of IFN-gamma and dexamethasone on TGF-beta1-induced human fetal lung fibroblast-myofibroblast differentiation. Acta Pharmacol Sin. 2004;25(11):1479-88.
Gu, L., Zhu, Y. J., Guo, Z. J., Xu, X. X., & Xu, W. B. (2004). Effect of IFN-gamma and dexamethasone on TGF-beta1-induced human fetal lung fibroblast-myofibroblast differentiation. Acta Pharmacologica Sinica, 25(11), 1479-88.
Gu L, et al. Effect of IFN-gamma and Dexamethasone On TGF-beta1-induced Human Fetal Lung Fibroblast-myofibroblast Differentiation. Acta Pharmacol Sin. 2004;25(11):1479-88. PubMed PMID: 15525471.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of IFN-gamma and dexamethasone on TGF-beta1-induced human fetal lung fibroblast-myofibroblast differentiation. AU - Gu,Li, AU - Zhu,Yuan-jue, AU - Guo,Zi-jian, AU - Xu,Xing-xiang, AU - Xu,Wen-bing, PY - 2004/11/5/pubmed PY - 2005/3/19/medline PY - 2004/11/5/entrez SP - 1479 EP - 88 JF - Acta pharmacologica Sinica JO - Acta Pharmacol Sin VL - 25 IS - 11 N2 - AIM: To study whether Smads signaling pathway was involved in human fetal lung fibroblast-myofibroblast differentiation induced by transforming growth factor (TGF)-beta1 and the role of interferon (IFN)-gamma, dexamethasone (DEX) in the fibroblast-myofibroblast differentiation. METHODS: Alpha-smooth muscle actin (alpha-SMA), Smad2/3, and Smad7 protein were assessed by Western blot. Collagen protein was analyzed by measuring hydroxyproline. Alpha-SMA and collagen III mRNA were assessed by RT-PCR. Myofibroblasts morphology and Smad2/3 nuclear translocation were assessed by immunohistochemistry. The overexpression of Smad7, a negative mediator of Smads signaling pathway, was acquired by transfection of Smad7 vector. RESULTS: During fibroblast-myofibroblast differentiation induced by TGF-beta1, IFN-gamma 200 microg/L markedly blocked TGF-beta1-induced alpha-SMA protein expression (P<0.01), collagen protein (P<0.01) and mRNA (P<0.05) expression, and myofibroblasts morphological transformation, but DEX 10 micromol/L augmented TGF-beta1-induced alpha-SMA expression (P<0.01). For myofibroblasts, both IFN-gamma 200 microg/L and DEX 10 micromol/L did not inhibit alpha-SMA expression (P>0.05) and collagen protein (P>0.05) and mRNA expression (P>0.05) and did not change myofibroblasts morphology. Transient transfection of Smad7 vector resulted in significant inhibition of TGF-beta1-induced alpha-SMA expression (P<0.01). IFN-gamma 200 microg/L did not block TGF-beta1-stimulated Smad2/3 phosphorylation and their nuclear translocation. CONCLUSION: TGF-beta1 induced fibroblast-myofibroblast differentiation in a Smad proteins-dependent manner. IFN-gamma could block this process but it was not mediated by interrupting smad2/3 phosphorylation and their nuclear translocation and DEX played a synergism with TGF-beta1. Differentiated myofibroblasts, however, were resistant to both IFN-gamma and DEX. SN - 1671-4083 UR - https://www.unboundmedicine.com/medline/citation/15525471/Effect_of_IFN_gamma_and_dexamethasone_on_TGF_beta1_induced_human_fetal_lung_fibroblast_myofibroblast_differentiation_ L2 - http://www.chinaphar.com/1671-4083/25/1479.pdf DB - PRIME DP - Unbound Medicine ER -