scholarly journals GW29-e0508 EGCG inhibits Angiotensin II-induced cardiac hypertrophy in H9C2 via activate HIPPO signaling pathway

2018 ◽  
Vol 72 (16) ◽  
pp. C82
Author(s):  
Yuan Ma ◽  
Jue Li
Bioimpacts ◽  
2019 ◽  
Vol 10 (4) ◽  
pp. 251-257
Author(s):  
Majid Gholipour ◽  
Arezoo Tabrizi

Introduction: The role of Hippo signaling pathway, which was identified by genetic studies as a key regulator for tissue growth and organ size, in promoting physiological cardiac hypertrophy has not been investigated. Methods: Fourteen male Wistar rats were randomly assigned to the exercise and control groups. The exercise group ran 1 hour per day, 5 days/week, at about 65%-75% VO2max on the motor-driven treadmill with 15º slope, and the control group ran 15 min/d, 2 days/week at 9 m/min (0º inclination), throughout the eight-week experimental period. Forty-eight hours after the last session, hearts were dissected and left ventricles were weighed and stored for subsequent RT-PCR analysis. Results: Despite a significant increase in the MAP4k1 expression levels in the exercise group (P = 0.001), the Mst1 expression was inhibited compared to the control group (P < 0.001) which was followed by suppression of Lats1 expression (P = 0.001). Compared with the control group, significant increases were observed in heart weight/body weight (P = 0.024) and left ventricular weight/body weight (P = 0.034) ratios in the exercise group. The H&E staining confirmed the cardiac hypertrophy that may be partly due to a significant increase in Yap1 expression level compared with the control group (P<0.001), which was confirmed by Western blot analysis. Conclusion: Increased MAP4K1 expression did not influence Lats1 activation. The exercise training protocol suppressed Mst1 and Lats1 (Hippo pathway) and caused an increase in Yap1 expression level, which led to physiological cardiac hypertrophy in healthy rats. Further studies are suggested to apply this exercise protocol for the prevention and/or rehabilitation of cardiovascular disease and health promotion.


Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
Wenfang Zheng ◽  
...  

Abstract Background Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC. Methods The expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1. Results Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression. Conclusions Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.


2021 ◽  
Vol 22 (2) ◽  
pp. 931
Author(s):  
Jihyun Lee ◽  
Yujin Jung ◽  
Seo won Jeong ◽  
Ga Hee Jeong ◽  
Gue Tae Moon ◽  
...  

The Hippo signaling pathway plays a key role in regulating organ size and tissue homeostasis. Hippo and two of its main effectors, yes-associated protein (YAP) and WWTR1 (WW domain-containing transcription regulator 1, commonly listed as TAZ), play critical roles in angiogenesis. This study investigated the role of the Hippo signaling pathway in the pathogenesis of rosacea. We performed immunohistochemical analyses to compare the expression levels of YAP and TAZ between rosacea skin and normal skin in humans. Furthermore, we used a rosacea-like BALB/c mouse model induced by LL-37 injections to determine the roles of YAP and TAZ in rosacea in vivo. We found that the expression levels of YAP and TAZ were upregulated in patients with rosacea. In the rosacea-like mouse model, we observed that the clinical features of rosacea, including telangiectasia and erythema, improved after the injection of a YAP/TAZ inhibitor. Additionally, treatment with a YAP/TAZ inhibitor reduced the expression levels of YAP and TAZ and diminished vascular endothelial growth factor (VEGF) immunoreactivity in the rosacea-like mouse model. Our findings suggest that YAP/TAZ inhibitors can attenuate angiogenesis associated with the pathogenesis of rosacea and that both YAP and TAZ are potential therapeutic targets for patients with rosacea.


2015 ◽  
Vol 57 (4) ◽  
pp. 341-351 ◽  
Author(s):  
Shinichi Hayashi ◽  
Hitoshi Yokoyama ◽  
Koji Tamura

Author(s):  
Yuanping Cao ◽  
Qun Wang ◽  
Caiyun Liu ◽  
Wenjun Wang ◽  
Songqing Lai ◽  
...  

Abstract Capn4 belongs to a family of calpains that participate in a wide variety of biological functions, but little is known about the role of Capn4 in cardiac disease. Here, we show that the expression of Capn4 was significantly increased in Angiotensin II (Ang II)-treated cardiomyocytes and Ang II-induced cardiac hypertrophic mouse hearts. Importantly, in agreement with the Capn4 expression patterns, the maximal calpain activity measured in heart homogenates was elevated in Ang II-treated mice, and oral coadministration of SNJ-1945 (calpain inhibitor) attenuated the total calpain activity measured in vitro. Functional assays indicated that overexpression of Capn4 obviously aggravated Ang II-induced cardiac hypertrophy, whereas Capn4 knockdown resulted in the opposite phenotypes. Further investigation demonstrated that Capn4 maintained the activation of the insulin-like growth factor (IGF)-AKT signaling pathway in cardiomyocytes by increasing c-Jun expression. Mechanistic investigations revealed that Capn4 directly bound and stabilized c-Jun, and knockdown of Capn4 increased the ubiquitination level of c-Jun in cardiomyocytes. Additionally, our results demonstrated that the antihypertrophic effect of Capn4 silencing was partially dependent on the inhibition of c-Jun. Overall, these data suggested that Capn4 contributes to cardiac hypertrophy by enhancing the c-Jun-mediated IGF-AKT signaling pathway and could be a potential therapeutic target for hypertrophic cardiomyopathy.


Cell Reports ◽  
2018 ◽  
Vol 25 (5) ◽  
pp. 1304-1317.e5 ◽  
Author(s):  
Yumeng Wang ◽  
Xiaoyan Xu ◽  
Dejan Maglic ◽  
Michael T. Dill ◽  
Kamalika Mojumdar ◽  
...  

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