Mechanisms of Induction of Airway Smooth Muscle Hyperplasia by Transforming Growth Factor-I?

Xie, S; Sukkar, M; Issa, R; Khorasani, N; Chung, K

Mechanisms of Induction of Airway Smooth Muscle Hyperplasia by Transforming Growth Factor-I?

Xie, S Sukkar, M Issa, R Khorasani, N Chung, K

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Publisher:: American Physiological Society
Publication Type:: Journal Article
Citation:: Khorasani, Nadia et al. 2007, 'Mechanisms of Induction of Airway Smooth Muscle Hyperplasia by Transforming Growth Factor-I?', American Journal of Physiology: Lung Cellular and Molecular Physiology, vol. 293, no. 1, pp. L245-L253.
Issue Date:: 2007

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Field	Value	Language
dc.contributor.author	Xie, S	en_US
dc.contributor.author	Sukkar, M	en_US
dc.contributor.author	Issa, R	en_US
dc.contributor.author	Khorasani, N	en_US
dc.contributor.author	Chung, K	en_US
dc.date.accessioned	2014-04-03T01:05:19Z
dc.date.available	2014-04-03T01:05:19Z
dc.date.issued	2007	en_US
dc.identifier	2011006540	en_US
dc.identifier.citation	Khorasani, Nadia et al. 2007, 'Mechanisms of Induction of Airway Smooth Muscle Hyperplasia by Transforming Growth Factor-I?', American Journal of Physiology: Lung Cellular and Molecular Physiology, vol. 293, no. 1, pp. L245-L253.	en_US
dc.identifier.issn	1040-0605	en_US
dc.identifier.other	C1UNSUBMIT	en_US
dc.identifier.uri	http://hdl.handle.net/10453/22151
dc.description.abstract	Because transforming growth factor (TGF)-I? is a potent regulator of ASM cell proliferation, we determined its expression and mitogenic signaling pathways in ASM cells. We obtained ASM cells by laser capture microdissection of bronchial biopsies and found that ASM cells from asthmatic patients expressed TGF-I?1 mRNA and protein to a greater extent than non-asthmatic individuals using real-time RTPCR and immunohistochemistry, respectively. TGF-I?1 stimulated the growth of non-confluent and confluent ASM cells either in the presence or absence of serum in a time- and concentration dependent manner. The mitogenic activity of TGF-I?1 on ASM cells was inhibited by selective inhibitors of TGF-I? receptor-I kinase (SD-208), of phosphatidylinositol 3-kinase (PI3K, LY294002), ERK (PD98059), JNK (SP600125) and NF-I?B (AS602868). On the other hand, p38 MAPK inhibitor (SB203580) augmented TGF-I?1-induced proliferation. To study role of the Smads, we transduced ASM cells with an adenovirus vector expressing Smad 4, Smad 7 or negative dominant Smad3 and found no involvement of these Smads in TGF-I?1-induced proliferation. Dexamethasone caused a dose-dependent inhibition in TGF-I?1-induced proliferation. Our findings suggest that TGF-I?1 may act in an autocrine fashion to induce ASM hyperplasia, mediated by its receptor and several kinases including PI3K, ERK and JNK, while p38 MAPK is a negative regulator. NF-I?B is also involved in the TGF-I?1 mitogenic signaling but Smad pathway does not appear important.	en_US
dc.publisher	American Physiological Society	en_US
dc.relation.ispartof	American Journal of Physiology: Lung Cellular and Molecular Physiology	en_US
dc.relation.ispartof	Verified OK	en_US
dc.relation.isbasedon	http://dx.doi.org/10.1152/ajplung.00068.2007	en_US
dc.subject	Laser capture microdissection; TGF-I?1 expression; airway smooth muscle cells; asthma; corticosteroids	en_US
dc.subject.classification	Physiology	en_US
dc.title	Mechanisms of Induction of Airway Smooth Muscle Hyperplasia by Transforming Growth Factor-I?	en_US
dc.type	Journal article
utslib.citation.volume	293	en_US
utslib.citation.number	1	en_US
utslib.location	Bethesda, MD, USA	en_US
utslib.citation.startpage	L245	en_US
utslib.citation.endpage	L253	en_US
utslib.identifier.org	GSH.Pharmacy	en_US
utslib.for	060600	en_US
utslib.percentage	50	en_US
utslib.copyright.status	closed_access

Abstract:

Because transforming growth factor (TGF)-I? is a potent regulator of ASM cell proliferation, we determined its expression and mitogenic signaling pathways in ASM cells. We obtained ASM cells by laser capture microdissection of bronchial biopsies and found that ASM cells from asthmatic patients expressed TGF-I?1 mRNA and protein to a greater extent than non-asthmatic individuals using real-time RTPCR and immunohistochemistry, respectively. TGF-I?1 stimulated the growth of non-confluent and confluent ASM cells either in the presence or absence of serum in a time- and concentration dependent manner. The mitogenic activity of TGF-I?1 on ASM cells was inhibited by selective inhibitors of TGF-I? receptor-I kinase (SD-208), of phosphatidylinositol 3-kinase (PI3K, LY294002), ERK (PD98059), JNK (SP600125) and NF-I?B (AS602868). On the other hand, p38 MAPK inhibitor (SB203580) augmented TGF-I?1-induced proliferation. To study role of the Smads, we transduced ASM cells with an adenovirus vector expressing Smad 4, Smad 7 or negative dominant Smad3 and found no involvement of these Smads in TGF-I?1-induced proliferation. Dexamethasone caused a dose-dependent inhibition in TGF-I?1-induced proliferation. Our findings suggest that TGF-I?1 may act in an autocrine fashion to induce ASM hyperplasia, mediated by its receptor and several kinases including PI3K, ERK and JNK, while p38 MAPK is a negative regulator. NF-I?B is also involved in the TGF-I?1 mitogenic signaling but Smad pathway does not appear important.

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http://hdl.handle.net/10453/22151