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Scleraxis is required for cell lineage differentiation and extracellular matrix remodeling during murine heart valve formation in vivo

宇晟添加于 2010-5-23 22:44 | 1113 次阅读 | 0 个评论

作者
Levay AK, Peacock JD, Lu Y, Koch M, Hinton RBJ, Kadler KE, Lincoln J
摘要
Heart valve structures, derived from mesenchyme precursor cells, are composed of differentiated cell types and extracellular matrix arranged to facilitate valve function. Scleraxis (scx) is a transcription factor required for tendon cell differentiation and matrix organization. This study identified high levels of scx expression in remodeling heart valve structures at embryonic day 15.5 through postnatal stages using scx-GFP reporter mice and determined the in vivo function using mice null for scx. Scx(-/-) mice display significantly thickened heart valve structures from embryonic day 17.5, and valves from mutant mice show alterations in valve precursor cell differentiation and matrix organization. This is indicated by decreased expression of the tendon-related collagen type XIV, increased expression of cartilage-associated genes including sox9, as well as persistent expression of mesenchyme cell markers including msx1 and snai1. In addition, ultrastructure analysis reveals disarray of extracellular matrix and collagen fiber organization within the valve leaflet. Thickened valve structures and increased expression of matrix remodeling genes characteristic of human heart valve disease are observed in juvenile scx(-/-) mice. In addition, excessive collagen deposition in annular structures within the atrioventricular junction is observed. Collectively, our studies have identified an in vivo requirement for scx during valvulogenesis and demonstrate its role in cell lineage differentiation and matrix distribution in remodeling valve structures.
详细资料
- 关键词: Aging; Animals; Basic Helix-Loop-Helix Transcription Factors/deficiency/genetics/*metabolism; Cartilage/embryology/metabolism; *Cell Differentiation/genetics; *Cell Lineage/genetics; Collagen/metabolism; Extracellular Matrix/genetics/*metabolism/ultrastructure; Fibrosis; Gene Expression Regulation, Developmental; Gestational Age; Glycoproteins/metabolism; Green Fluorescent Proteins/metabolism; Heart Valve Diseases/embryology/metabolism; Heart Valves/embryology/growth & development/*metabolis
- 文献种类:期刊
- 期刊名称: Circulation Research
- 期刊缩写: Circ Res
- 期卷页: 2008年第103卷第9期 948-956页
- 地址: Department of Molecular and Cellular Pharmacology, Leonard M Miller School of Medicine, University of Miami, Miami, FL 33101, USA
- ISBN: 0009-7330
- 备注:PMID:18802027
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宇晟的文献笔记订阅

tendon and heart valve

In this paper，the author reported an in vivo requirement for scleraxis (scx) during murine valvulogenesis and demonstrate its role in cell lineage differentiation and matrix distribution in remodeling valve structures。Scleraxis is a transcription factor required for tendon cell differentiation and matrix organization.This group determined the in vivo function of scx using null mice (scx^-/-). Thickened valve structures and increased expression of matrix remodeling genes characteristic of human heart valve disease, are observed in juvenile scx^{- /-} mice. Thus, mice null for scx exhibit pathological criteria common to diseased valves from embryonic stages, and by juvenile stages express high levels of fibrosis-associated genes and matrix proteases previously observed in human valve pathology. Taken together, these findings add to increasing evidence that valve disease associated with alterations in ECM has its origins in valve development.

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