Browsing by Author "Wu, Chien-Liang"

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Alternative Roles of STAT3 and MAPK Signaling Pathways in the MMPs Activation and Progression of Lung Injury Induced by Cigarette Smoke Exposure in ACE2 Knockout Mice
(2016-01-01)
Hung, Yi-Han
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Hsieh, Wen-Yeh
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Hsieh, Jih-Sheng
;
Liu, Fon-Chang
;
Tsai, Chin-Hung
Inflammation-mediated abnormalities in the renin-angiotensin system (RAS) and expression of matrix metalloproteinases (MMPs) are implicated in the pathogenesis of lung injury. Angiotensin converting enzyme II (ACE2), an angiotensin converting enzyme (ACE) homologue that displays antagonist effects on ACE/angiotensin II (Ang II) axis, could also play a protective role against lung diseases. However, the relationship between ACE2 and MMPs activation in lung injury is still largely unclear. The purpose of this study is to investigate whether MMPs activity could be affected by ACE2 and which ACE2 derived signaling pathways could be also involved via using a mouse model with lung injury induced by cigarette smoke (CS) exposure for 1 to 3 weeks. Wild-type (WT; C57BL/6) and ACE2 KO mice (ACE2(-/-)) were utilized to study CS-induced lung injury. Increases in the resting respiratory rate (RRR), pulmonary immunokines, leukocyte infiltration and bronchial hyperplasia were observed in the CS-exposed mice. Compared to WT mice, more serious physiopathological changes were found in ACE2(-/-) mice in the first week of CS exposure. CS exposure increased pulmonary ACE and ACE2 activities in WT mice, and significantly increased ACE in ACE2(-/-) mice. Furthermore, the activity of pulmonary MMPs was decreased in CS-exposed WT mice, whereas this activity was increased in ACE2(-/-) mice. CS exposure increased the pulmonary p-p38, p-JNK and p-ERK1/2 level in all mice. In ACE2(-/-) mice, a significant increase p-STAT3 signaling was detected; however, no effect was observed on the p-STAT3 level in WT mice. Our results support the hypothesis that ACE2 deficiency influences MMPs activation and STAT3 phosphorylation signaling to promote more pulmonary inflammation in the development of lung injury.
Angiotensin II downregulates ACE2-mediated enhancement of MMP-2 activity in human cardiofibroblasts
(2013-12-01)
Kuan, Tang-Ching
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Chen, Mu-Yuan
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Liao, Yan-Chiou
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Ko, Li
;
Hong, Yi-Han
Angiotensin converting enzyme II (ACE2) is a component of the renin-angiotensin system (RAS) that negatively regulates angiotensin II (Ang II). Ang II, in turn, affects the expression of matrix metalloproteinases (MMPs) to induce heart remodeling. The specific mechanisms by which ACE2 regulates MMP-2, however, remain unclear. The aim of this study was to investigate the regulatory relationships between Ang II, ACE2, and MMP-2. ACE2 expression was upregulated and downregulated in human cardiofibroblasts (HCFs) by lentiviral infection. Effects on MMP-2 activity, shed ACE2 activity, extracellular signal-regulated kinase (ERK) signaling pathway, and ADAM metallopeptidase domain 17 (ADAM17) expression were assessed. ACE2 increased MMP-2 activity, and Ang II inhibited this effect through the Ang II type-1 receptor (AT1R) and ERK1/2 signaling pathway. Ang II also reduced the effect of ACE2 on ERK1/2 levels, the activity of shed ACE2, and adam17 expression in HCFs. Additionally, these Ang II-mediated reductions could be attenuated by AT1R antagonist valsartan. In conclusion, these data help to clarify how ACE2 and Ang II interact to regulate MMP-2 and control tissue remodeling in heart disease.
Circulating Matrix Metalloproteinase-2 and-9 Enzyme Activities in the Children with Ventricular Septal Defect
(2013)
Cheng, Kun-Shan
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Liao, Yan-Chiou
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Chen, Mu-Yuan
;
Kuan, Tang-Ching
;
Hong, Yi-Han
Ventricular septal defect (VSD) is the most common form of congenital heart diseases. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases involved in causal cardiac tissue remodeling. We studied the changes of circulating MMP-2 and MMP-9 activities in the patients with VSD severity and closure. There were 96 children with perimembranous VSD enrolled in this study. We assigned the patients into three groups according to the ratio of VSD diameter/diameter of aortic root (Ao). They were classified as below: Trivial (VSD/Ao ratio <= 0.2), Small (0.2 < VSD/Ao <= 0.3) and Median (0.3 < VSD/Ao) group. Plasma MMP-2 and MMP-9 activities were assayed by gelatin zymography. There was a significant higher MMP-2 activity in the VSD (Trivial, Small and Median) groups compared with that in Control group. The plasma MMP-9 activity showed a similar trend as the findings in MMP-2 activity. After one year follow-up, a significant difference in the MMP-9 activity was found between VSD spontaneous closure and non-closure groups. In conclusion, a positive trend between the severity of VSD and activities of MMP-2 and MMP-9 was found. Our data imply that MMP-2 and MMP-9 activities may play a role in the pathogenesis of VSD.
Design and Study of a Portable High-frequency Ventilator for Clinical Applications
(2019-01-01)
Lu, Shao-Yung
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Lin, Hau
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Kuo, Hsu-Tah
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Wu, Chien-Liang
;
Wu, Wen-Jui
Treatment costs for ventilator-dependent patients are a substantial burden not only for their family but also for medical systems in general. Recently, using high-frequency ventilators have been shown to reduce the risk of lung injury through low-volume airflow. However, the machines used today remain bulky, costly, and only for use in hospital settings. To provide intermediate therapy for patients between hospitalization and complete discharge, a portable, light-weight high-frequency ventilator is an urgent need. This work presents the design of a portable high-frequency ventilator and a study of its practicality for further clinical medical applications. Through the integration of advanced electronics and mechanical instruments, we develop a portable high-frequency ventilator with reconfigurable oxygen flow rate, applied pressure, and air volume for the needs of individual patients. A miniaturized portable high-frequency ventilator with digital controller and feedback system for stabilization and precision control is implemented. The efficiency of CO2 washout using the proposed ventilator has been demonstrated in animal trials.
Highly textured ZnO:B films grown by low pressure chemical vapor deposition for efficiency enhancement of heterojunction silicon-based solar cells
(2013-09-01)
Hsiao, Jui-Chung
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Chen, Chien-Hsun
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Yang, Hung-Jen
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Wu, Chien-Liang
;
Fan, Chia-Ming
This paper demonstrates the growth of highly-textured boron-doped ZnO (ZnO:B) film by using low-pressure chemical-vapor-deposition (LPCVD) for efficient light harvesting and carrier collection in heterojunction silicon-based (HJS) solar cells. The optical and electrical characteristics have been optimized versus the substrate temperature and B2H6 flow rate for tradeoffs among the sheet resistance, free-carrier absorption, and optical transmission of blue/green wavelengths. A HJS solar cell with a 1.6-mu m-thick ZnO:B film achieves a high power conversion efficiency of 16.30% and fill factor of 78.05%, compared to 15.64% and 72.17%, respectively, from a counterpart with a conventional 80-nm-thick indium tin oxide layer. (C) 2013 Taiwan Institute of Chemical Engineers. Published by Elsevier B.V. All rights reserved.