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学科主题临床医学
Prostacyclin analogs inhibit fibroblast contraction of collagen gels through the cAMP-PKA pathway
Kamio, Koichiro1; Liu, Xiangde1; Sugiura, Hisatoshi1; Togo, Shinsaku1; Kobayashi, Tetsu1; Kawasaki, Shinsaku1; Wang, Xingqi1; Mao, Lijun1; Ahn, Youngsoo1; Hogaboam, Cory1; Toews, Myron L.1; Rennard, Stephen I.1
关键词Prostacyclin Fibroblasts Tissue Remodeling Fibronectin
刊名AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
2007-07-01
DOI10.1165/rcmb.2007-0009OC
37期:1页:113-120
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Cell Biology ; Respiratory System
研究领域[WOS]Biochemistry & Molecular Biology ; Cell Biology ; Respiratory System
关键词[WOS]PULMONARY ARTERIAL-HYPERTENSION ; DEPENDENT PROTEIN-KINASE ; PROSTANOID RECEPTORS ; WOUND CONTRACTION ; LUNG FIBROBLASTS ; CYCLIC-AMP ; FIBRONECTIN ; CELLS ; ACTIVATION ; LATTICES
英文摘要

Prostacyclin is an arachidonic acid metabolite that modulates vascular tone within the lung. The current study evaluated the hypothesis that prostacyclin can also modulate tissue remodeling by affecting fibroblast-mediated contraction of extracellular matrix. To accomplish this, fibroblasts were cultured in three-dimensional native type I Collagen gels in the presence of prostacyclin analogs: carbaprostacyclin, iloprost, and beraprost. All three analogs significantly inhibited contraction of the three-dimensional collagen gels mediated by three different fibroblasts. All three analogs significantly inhibited fibronectin release and reduced fibroblast fibronectin mRNA expression. Addition of exogenous fibronectin restored the contractile activity to fibroblasts incubated in the presence of all three analogs. Iloprost and beraprost significantly activated cAMP-dependent protein kinase-A (PKA), and an action through this pathway was confirmed by blockade of the inhibitory effect on contraction and fibronectin release with the PKA inhibitor KT-5720. In contrast, carbaprostacyclin, which is not as selective for the prostacyclin (IP) receptor, did not activate PKA, and its effects on contraction and fibronectin release were not fully blocked by KT-5720. Finally, the CAMP analogs N-6-Benzoyl-(6-Bnz-) cAMP and dibutyryl-cAMP inhibited contraction, and this contrasted with the activity of an Epac selective agonist 8-pCPT-2′-O-Me-cAMP, which had no effect. Taken together, these results indicate that prostacyclin, acting through the IP receptor and by activating PKA, can lead to inhibition of fibronectin release and can subsequently inhibit fibroblast-mediated Collagen gel contraction. The ability of prostacyclin to modulate fibroblast function suggests that prostacyclin can contribute to tissue remodeling.

语种英语
WOS记录号WOS:000247661500014
引用统计
被引频次:18[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52829
专题北京大学第三临床医学院_风湿免疫科
作者单位1.Wakayama Med Univ, Dept Internal Med 3, Wakayama, Japan
2.Mie Univ, Grad Sch Med, Dept Internal Med, Tsu, Mie 514, Japan
3.Univ Nebraska, Med Ctr, Dept Pulm & Crit Care Med, Omaha, NE 68198 USA
4.Univ Nebraska, Med Ctr, Dept Pharmacol, Omaha, NE 68198 USA
5.Univ Michigan, Sch Med, Dept Pathol, Program Immunol, Ann Arbor, MI 48109 USA
6.Peking Univ, Hosp 3, Dept Rheumatol, Beijing 100871, Peoples R China
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GB/T 7714
Kamio, Koichiro,Liu, Xiangde,Sugiura, Hisatoshi,et al. Prostacyclin analogs inhibit fibroblast contraction of collagen gels through the cAMP-PKA pathway[J]. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY,2007,37(1):113-120.
APA Kamio, Koichiro.,Liu, Xiangde.,Sugiura, Hisatoshi.,Togo, Shinsaku.,Kobayashi, Tetsu.,...&Rennard, Stephen I..(2007).Prostacyclin analogs inhibit fibroblast contraction of collagen gels through the cAMP-PKA pathway.AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY,37(1),113-120.
MLA Kamio, Koichiro,et al."Prostacyclin analogs inhibit fibroblast contraction of collagen gels through the cAMP-PKA pathway".AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY 37.1(2007):113-120.
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