Browsing by Author "Liu, Fon-Chang"

Now showing 1 - 2 of 2

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
;
Hsieh, Wen-Yeh
;
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.
Matrix metalloproteinase 2 level in human follicular fluid is a reliable marker of human oocyte maturation in in vitro fertilization and intracytoplasmic sperm injection cycles
(2015-09-04)
Yang, Wen-Jui
;
Liu, Fon-Chang
;
Hsieh, Jih-Sheng
;
Chen, Ching-Hung
;
Hsiao, Shun-Yu
Background: To determine whether matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMP-1 and TIMP-2) in human follicular fluid, have any relationships with oocyte maturation in vivo and subsequent fertilization during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles. Methods: The follicular fluids were obtained from 150 female patients undergoing IVF/ICSI cycles and a total of 1504 oocytes were retrieved for analysis. MMP-2 and MMP-9 activities were measured using zymography assay. TIMP-1 and TIMP-2 concentrations were quantitatively assessed using enzyme-linked immunosorbent assay (ELISA). Results: Human follicular fluid MMP-2 level was significantly associated with the rate of maturity of oocytes (P < 0.001). Furthermore, the MMP-2 was significantly associated with the higher fertilization rate (P < 0.01). There was no significant correlation between follicular MMP-9 and the maturation rate of oocytes. The TIMP-1 and TIMP-2 also showed no correlation with the oocyte maturation rate. Conclusions: The level of gelatinase MMP-2 in human follicular fluid might be a reliable marker of mature oocytes during IVF/ICSI cycles. Furthermore, the MMP-2 expression has a strong association with higher fertilization rate. Further studies are needed to support this theory.