TGF-β stimulates biglycan synthesis via p38 and ERK phosphorylation of the linker region of Smad2

被引：84

作者：

Burch, Micah L. ^{[2
,3
,4
]}

Yang, Sundy N. Y. ^{[2
]}

Ballinger, Mandy L. ^{[2
]}

Getachew, Robel ^{[2
]}

Osman, Narin ^{[2
,3
,4
]}

Little, Peter J. ^{[1
,2
,3
,4
]}

机构：

[1] Baker IDI Heart & Diabet Inst, Diabet & Cell Biol Lab, Melbourne, Vic 8008, Australia

[2] Baker IDI Heart & Diabet Inst, Diabet & Cell Biol Lab, Melbourne, Vic 3004, Australia

[3] Monash Univ, Alfred Hosp, Sch Med, Dept Med, Prahran, Vic 3004, Australia

[4] Monash Univ, Alfred Hosp, Sch Med, Dept Immunol, Prahran, Vic 3004, Australia

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2010年 / 67卷 / 12期

基金：

英国医学研究理事会;

关键词：

MAP kinases; Transforming growth factor-beta; Glycosaminoglycan; Atherosclerosis; Biglycan; GROWTH-FACTOR-BETA; ARTERIAL SMOOTH-MUSCLE; PROTEOGLYCAN SYNTHESIS; INCREASED BINDING; EXPRESSION; CELLS; ATHEROSCLEROSIS; LIPOPROTEINS; DOWNSTREAM; ACTIVATION;

D O I：

10.1007/s00018-010-0315-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Transforming growth factor (TGF)-beta treatment of human vascular smooth-muscle cells increases the expression of biglycan and causes marked elongation of its glycosaminoglycan (GAG) chains. We investigated the role of MAP kinases and Smad transcription factors in this response. TGF-beta-stimulated phosphorylation of p38, ERK, and JNK as well as Smad2 at both its carboxy terminal (phospho-Smad2C) and in the linker region (phospho-Smad2L). Pharmacological inhibition of ERK and p38 blocked TGF-beta-mediated GAG elongation and expression of biglycan whereas inhibition of JNK had no effect. Inhibition of ERK and p38 but not JNK attenuated the effect of TGF-beta to increase phospho-Smad2L. High levels of phospho-Smad2L were detected in a nuclear fraction of TGF-beta treated cells. Thus, MAP kinase signaling through ERK and p38 and via phosphorylation of the linker region of Smad2 mediates the effects of TGF-beta on biglycan synthesis in vascular smooth-muscle cells.

引用

页码：2077 / 2090

页数：14

共 43 条

[1]

Agrotis Alex, 2005, Current Vascular Pharmacology, V3, P55, DOI 10.2174/1570161052773951

[2]

Imatinib inhibits vascular smooth muscle proteoglycan synthesis and reduces LDL binding in vitro and aortic lipid deposition in vivo [J].

Ballinger, Mandy L. ;

Osman, Narin ;

Hashimura, Kazuhiko ;

de Haan, Judy B. ;

Jandeleit-Dahm, Karin ;

Allen, Terri ;

Tannock, Lisa R. ;

Rutledge, John C. ;

Little, Peter J. .

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2010, 14 (6B) :1408-1418

[3]

Endothelin-1 activates ETA receptors on human vascular smooth muscle cells to yield proteoglycans with increased binding to LDL [J].

Ballinger, Mandy L. ;

Ivey, Melanie E. ;

Osman, Narin ;

Thomas, Walter G. ;

Little, Peter J. .

ATHEROSCLEROSIS, 2009, 205 (02) :451-457

[4]

Regulation of glycosaminoglycan structure and atherogenesis [J].

Ballinger, ML ;

Nigro, J ;

Frontanilla, KV ;

Dart, AM ;

Little, PJ .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2004, 61 (11) :1296-1306

[5]

Distinct patterns of transforming growth factor-β isoform and receptor expression in human atherosclerotic lesions -: Colocalization implicates TGF-β in fibrofatty lesion development [J].

Bobik, A ;

Agrotis, A ;

Kanellakis, P ;

Dilley, R ;

Krushinsky, A ;

Smirnov, V ;

Tararak, E ;

Condron, M ;

Kostolias, G .

CIRCULATION, 1999, 99 (22) :2883-2891

[6]

CAMEJO G, 1982, ADV LIPID RES, V19, P1

[7]

CHANG Y, 1983, J BIOL CHEM, V258, P5679

[8]

Smad and p38 MAP kinase-mediated signaling of proteoglycan synthesis in vascular smooth muscle [J].

Dadlani, Harsha ;

Ballinger, Mandy L. ;

Osman, Narin ;

Getachew, Robel ;

Little, Peter J. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (12) :7844-7852

[9]

Smad-dependent and Smad-independent pathways in TGF-β family signalling [J].

Derynck, R ;

Zhang, YE .

NATURE, 2003, 425 (6958) :577-584

[10]

Pharmacotherapy of coronary atherosclerosis [J].

Finn, Aloke V. ;

Kramer, Miranda C. A. ;

Vorpahl, Marc ;

Kolodgie, Frank D. ;

Virmani, Renu .

EXPERT OPINION ON PHARMACOTHERAPY, 2009, 10 (10) :1587-1603

← 1 2 3 4 5 →