JOURNAL ARTICLE

Effect of IFN-gamma and dexamethasone on TGF-beta1-induced human fetal lung fibroblast-myofibroblast differentiation

Li Gu, Yuan-jue Zhu, Zi-jian Guo, Xing-xiang Xu, Wen-bing Xu
Acta Pharmacologica Sinica 2004, 25 (11): 1479-88
15525471

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.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
15525471
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"