Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension

被引：10

作者：

Seki, Mitsuru ^{[1
,2
,3
]}

Furukawa, Nozomi ^{[2
]}

Koitabashi, Norimichi ^{[2
]}

Obokata, Masaru ^{[2
]}

Conway, Simon J. ^{[4
]}

Arakawa, Hirokazu ^{[1
]}

Kurabayashi, Masahiko ^{[2
]}

机构：

[1] Gunma Univ, Grad Sch Med, Dept Pediat, Maebashi, Gunma, Japan

[2] Gunma Univ, Grad Sch Med, Dept Cardiovasc Med, Maebashi, Gunma, Japan

[3] Jichi Med Univ, Dept Pediat, Shimotsuke, Tochigi, Japan

[4] Indiana Univ Sch Med, Herman B Wells Ctr Pediat Res, Indianapolis, IN 46202 USA

来源：

PLOS ONE | 2019年 / 14卷 / 08期

基金：

日本学术振兴会; 美国国家卫生研究院;

关键词：

BONE MORPHOGENETIC PROTEIN; OSTEOBLAST-SPECIFIC FACTOR; SMOOTH-MUSCLE-CELLS; TGF-BETA; RECEPTOR; PROLIFERATION; PROGRESSION; MUTATIONS;

D O I：

10.1371/journal.pone.0220795

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Transforming growth factor beta (TGF-beta) has been shown to play a critical role in pathogenesis of pulmonary arterial hypertension (PAH) although the precise role of TGF-beta signaling remains uncertain. A recent report has shown that periostin (Pn) is one of the most upregulated proteins in human PAH lung compared with healthy lungs. We established type I TGF-beta receptor knockout mice specifically with Pn expressing cell (Pn-Cre/Tgfb1(fl/fl) mice). Increases in PA pressure and pulmonary artery muscularization were induced by hypoxia of 10% oxygen for 4 weeks. Lung Pn expression was markedly induced by 4 week-hypoxia. Pn-Cre/Tgfb1(fl/fl) mice showed lower right ventricular pressure elevation, inhibition of PA medial thickening. Fluorescent co-immunostaining showed that Smad3 activation in Pn expressing cell is attenuated. These results suggest that TGF-beta signaling in Pn expressing cell may have an important role in the pathogenesis of PAH by controlling medial thickening.

引用

页数：13

共 40 条

[1] Proteomic Analysis of Lung Tissues From Patients With Pulmonary Arterial Hypertension [J].

Abdul-Salam, Vahitha B. ;

Wharton, John ;

Cupitt, John ;

Berryman, Mark ;

Edwards, Robert J. ;

Wilkins, Martin R. .

CIRCULATION, 2010, 122 (20) :2058-U282

[2] Periostin regulates fibrocyte function to promote myofibroblast differentiation and lung fibrosis [J].

Ashley, S. L. ;

Wilke, C. A. ;

Kim, K. K. ;

Moore, B. B. .

MUCOSAL IMMUNOLOGY, 2017, 10 (02) :341-351

[3] Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway [J].

Bao, SD ;

Ouyang, G ;

Bai, XF ;

Huang, Z ;

Ma, CY ;

Liu, M ;

Shoo, R ;

Anderson, RM ;

Rich, JN ;

Wang, XF .

CANCER CELL, 2004, 5 (04) :329-339

[4] The role of periostin in tissue remodeling across health and disease [J].

Conway, Simon J. ;

Izuhara, Kenji ;

Kudo, Yasusei ;

Litvin, Judith ;

Markwald, Roger ;

Ouyang, Gaoliang ;

Arron, Joseph R. ;

Holweg, Cecile T. J. ;

Kudo, Akira .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2014, 71 (07) :1279-1288

[5] Periostin as a Heterofunctional Regulator of Cardiac Development and Disease [J].

Conway, Simon J. ;

Molkentin, Jeffery D. .

CURRENT GENOMICS, 2008, 9 (08) :548-555

[6] Hypoxia-induced pulmonary artery adventitial remodeling and neovascularization: contribution of progenitor cells [J].

Davie, NJ ;

Crossno, JT ;

Frid, MG ;

Hofmeister, SE ;

Reeves, JT ;

Hyde, DM ;

Carpenter, TC ;

Brunetti, JA ;

McNiece, IK ;

Stenmark, KR .

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2004, 286 (04) :L668-L678

[7] BMP type II receptor deficiency confers resistance to growth inhibition by TGF-β in pulmonary artery smooth muscle cells: role of proinflammatory cytokines [J].

Davies, Rachel J. ;

Holmes, Alan M. ;

Deighton, John ;

Long, Lu ;

Yang, Xudong ;

Barker, Lucy ;

Walker, Christoph ;

Budd, David C. ;

Upton, Paul D. ;

Morrell, Nicholas W. .

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2012, 302 (06) :L604-L615

[8] Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene [J].

Deng, ZM ;

Morse, JH ;

Slager, SL ;

Cuervo, N ;

Moore, KJ ;

Venetos, G ;

Kalachikov, S ;

Cayanis, E ;

Fischer, SG ;

Barst, RJ ;

Hodge, SE ;

Knowles, JA .

AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 67 (03) :737-744

[9] Mature vascular endothelium can give rise to smooth muscle cells via endothelial-mesenchymal transdifferentiation - In vitro analysis [J].

Frid, MG ;

Kale, VA ;

Stenmark, KR .

CIRCULATION RESEARCH, 2002, 90 (11) :1189-1196

[10] Primary pulmonary hypertension [J].

Gaine, SP ;

Rubin, LJ .

LANCET, 1998, 352 (9129) :719-725

← 1 2 3 4 →