کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2463793 1111749 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Developmental pathways and endothelial to mesenchymal transition in canine myxomatous mitral valve disease
ترجمه فارسی عنوان
مسیرهای رشد و اندوتلیال به انتقال مزانشیمال در بیماری دریچه میتریک دریچه سینه
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم دامی و جانورشناسی
چکیده انگلیسی


• The first report of development signalling pathways and endothelial to mesenchymal transition in myxomatous mitral valve disease.
• Recognises mechanisms previously reported for fibrotic conditions and cancer metastasis, rather than a degenerative condition.
• Information is provided on biological mechanisms that have therapeutic potential for new drug discovery.

Epithelial to mesenchymal transition (EMT) and the cardiovascular equivalent, endothelial to mesenchymal transition (EndoMT), contribute to a range of chronic degenerative diseases and cancer metastasis. Chronic valvulopathies exhibit some features of EndoMT and activation of developmental signalling pathways, such as osteogenesis and chondrogenesis, expression of cell differentiation markers, basement membrane damage and endothelial transformation. The aim of the present study was to investigate the potential role of developmental mechanisms in canine myxomatous mitral valve disease (MMVD) using a combination of transcriptomic array technology, RT-PCR and immunohistochemistry.There was significant differential expression for genes typically associated with valvulogenesis and EndoMT, including markers of inflammation (IL6, IL18 and TLR4), basement membrane disarray (NID1, LAMA2 and CTSS), mesenchymal and endothelial cell differentiation (MYH11 and TAGLN) and EndoMT (ACTA2, SNAI1, CTNNB1, HAS2, CDH5, and NOTCH1), with fold changes from +15.35 (ACTA2) to −5.52 (LAMA2). These changes in gene expression were confirmed using RT-PCR, except for HAS2. In silico analysis identified important gene networks and canonical pathways in MMVD that have associations with development and organogenesis, including inflammation, valve morphogenesis and EMT, as well as components of the basement membrane and extra-cellular matrix. Immunohistochemistry identified changes in the expression of hyaluronic acid synthase (Has2), Snai1, α-smooth muscle actin (α-SMA) and VE-cadherin (CDH5), and co-expression of Has2 with α-SMA. These research findings strongly suggest involvement of developmental signalling pathways and mechanisms, including EndoMT, in the pathogenesis of canine MMVD.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Veterinary Journal - Volume 206, Issue 3, December 2015, Pages 377–384
نویسندگان
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