학술논문
Notch signaling may negatively regulate neonatal rat cardiac fibroblast-myofibroblast transformation
Document Type
TEXT
Author
Source
Physiological research | 2011 Volume:60 | Number:5
Subject
Language
English
Abstract
Y.-H. Fan ... [et al.].
Obsahuje bibliografii a bibliografické odkazy
Cardiac fibroblast-myofibroblast transformation (CMT) is a critical event in the initiation of myocardial fibrosis. Notch signaling has been shown to regulate myofibroblast transformation from other kinds of cells. However, whether Notch signaling is also involved in CMT remains unclear. In the present study, expressions of Notch receptors in cardiac fibroblasts (CFs) were examined, effects of Notch signaling inhibi tor N-[N-(3,5-difluorophenacetyl)- l-alanyl]-S-phenylglycine t-butyl ester (DAPT) and transforming growth factor-β1 (TGF-β1) on CMT were determined by increasing alpha-smooth muscle actin (α-SMA) expression and collagen synthesis, and Notch signaling was examined by analyzing expressions of Notch receptors. The results showed that: (1) Notch receptor 1, 2, 3 and 4 were all expressed in CFs; (2) DAPT promoted CMT in a time -dependent manner; (3) During the period of CMT induced by TGF-β1, expressions of Notch receptor 1, 3 and 4 in CFs were down-regulated, whereas there was no change for Notch receptor 2. Moreover, the downtrends of Notch 1, 3 and 4 were corresponding to the trend growth of α-SMA expression and collagen synthesis. These results suggested that inhibiting of Notch signaling might promote CMT. The down-regulations of Notch receptor 1, 3 and 4 induced by TGF-β1 may facilitate CMT. In conclusion, inhibition of Notch signaling might be a novel mech anism of CMT in myocardial fibrosis.
Obsahuje bibliografii a bibliografické odkazy
Cardiac fibroblast-myofibroblast transformation (CMT) is a critical event in the initiation of myocardial fibrosis. Notch signaling has been shown to regulate myofibroblast transformation from other kinds of cells. However, whether Notch signaling is also involved in CMT remains unclear. In the present study, expressions of Notch receptors in cardiac fibroblasts (CFs) were examined, effects of Notch signaling inhibi tor N-[N-(3,5-difluorophenacetyl)- l-alanyl]-S-phenylglycine t-butyl ester (DAPT) and transforming growth factor-β1 (TGF-β1) on CMT were determined by increasing alpha-smooth muscle actin (α-SMA) expression and collagen synthesis, and Notch signaling was examined by analyzing expressions of Notch receptors. The results showed that: (1) Notch receptor 1, 2, 3 and 4 were all expressed in CFs; (2) DAPT promoted CMT in a time -dependent manner; (3) During the period of CMT induced by TGF-β1, expressions of Notch receptor 1, 3 and 4 in CFs were down-regulated, whereas there was no change for Notch receptor 2. Moreover, the downtrends of Notch 1, 3 and 4 were corresponding to the trend growth of α-SMA expression and collagen synthesis. These results suggested that inhibiting of Notch signaling might promote CMT. The down-regulations of Notch receptor 1, 3 and 4 induced by TGF-β1 may facilitate CMT. In conclusion, inhibition of Notch signaling might be a novel mech anism of CMT in myocardial fibrosis.