scholarly journals β-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in Hypertensive Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Catherina A. Cuevas ◽  
Cheril Tapia-Rojas ◽  
Carlos Cespedes ◽  
Nibaldo C. Inestrosa ◽  
Carlos P. Vio
Keyword(s):  
Blood Pressure ◽  
Signal Transduction ◽  
Single Dose ◽  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Target Genes ◽  
Hypertensive Rats ◽  
Collagen Types ◽  
Dependent Signaling Pathway ◽  
Pyrvinium Pamoate

The mechanism of hypertension-induced renal fibrosis is not well understood, although it is established that high levels of angiotensin II contribute to the effect. Sinceβ-catenin signal transduction participates in fibrotic processes, we evaluated the contribution ofβ-catenin-dependent signaling pathway in hypertension-induced renal fibrosis. Two-kidney one-clip (2K1C) hypertensive rats were treated with lisinopril (10 mg/kg/day for four weeks) or with pyrvinium pamoate (Wnt signaling inhibitor, single dose of 60 ug/kg, every 3 days for 2 weeks). The treatment with lisinopril reduced the systolic blood pressure from 220 ± 4 in 2K1C rats to 112 ± 5 mmHg (P<0.05), whereas the reduction in blood pressure with pyrvinium pamoate was not significant (212 ± 6 in 2K1C rats to 170 ± 3 mmHg,P>0.05). The levels of collagen types I and III, osteopontin, and fibronectin decreased in the unclipped kidney in both treatments compared with 2K1C rats. The expressions ofβ-catenin, p-Ser9-GSK-3beta, and theβ-catenin target genes cyclin D1, c-myc, and bcl-2 significantly decreased in unclipped kidney in both treatments (P<0.05). In this study we provided evidence thatβ-catenin-dependent signaling pathway participates in the renal fibrosis induced in 2K1C rats.

scholarly journals Corrigendum to “β-Catenin-Dependent Signaling Pathway Contributes to Renal Fibrosis in Hypertensive Rats”

2016 ◽  
Vol 2016 ◽  
pp. 1-2
Author(s):  
Catherina A. Cuevas ◽  
Cheril Tapia-Rojas ◽  
Carlos Cespedes ◽  
Nibaldo C. Inestrosa ◽  
Carlos P. Vio
Keyword(s):  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Hypertensive Rats ◽  
Dependent Signaling Pathway

scholarly journals Pyrvinium pamoate inhibits cell proliferation through ROS-mediated AKT-dependent signaling pathway in colorectal cancer

2021 ◽  
Vol 38 (2) ◽  
Author(s):  
Wenqian Zheng ◽  
Jinhui Hu ◽  
Yiming Lv ◽  
Bingjun Bai ◽  
Lina Shan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
Flow Cytometric Analysis ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Dependent Signaling Pathway ◽  
Pyrvinium Pamoate

AbstractThe use of the anthelmintic drug pyrvinium pamoate (PP) in cancer therapy has been extensively investigated in the last decade. PP has been shown to have an inhibitory effect in colorectal cancer (CRC), but the underlying mechanism remains elusive. We aimed to investigate the antitumor activity and mechanisms of PP in CRC. In the present study, we used CCK-8 assays, colony formation assays, and western blotting to reveal that PP effectively suppressed CRC cell proliferation and the AKT-dependent signaling pathway in a concentration-dependent and time-dependent manner. Flow cytometric analysis and fluorescence microscopy demonstrated that PP increased intracellular reactive oxygen species (ROS) accumulation. We found that the inhibitory effect of PP on cell proliferation and AKT protein expression induced by PP could be partially reversed by N-acetyl-l-cysteine (NAC), an ROS scavenger. In addition, the results also demonstrated that PP inhibited cell migration by modulating epithelial-to-mesenchymal transition (EMT)-related proteins, including E-cadherin and vimentin. In conclusion, our data suggested that PP effectively inhibited cell proliferation through the ROS-mediated AKT-dependent signaling pathway in CRC, further providing evidence for the use of PP as an antitumor agent.

scholarly journals TNF-α- Mediated-p38-Dependent Signaling Pathway Contributes to Myocyte Apoptosis in Rats Subjected to Surgical Trauma

2015 ◽  
Vol 35 (4) ◽  
pp. 1454-1466 ◽  
Author(s):  
Huaxing Wu ◽  
Guonian Wang ◽  
Shuai Li ◽  
Mingyue Zhang ◽  
Hulun Li ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Flow Cytometry ◽  
Signaling Pathway ◽  
Early Stage ◽  
Surgical Trauma ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Myocyte Apoptosis ◽  
Dependent Signaling Pathway

Background: The accumulation of cytokines in the plasma after trauma can induce myocyte apoptosis. We aimed to identify which cytokine(s) present in the plasma responsible for myocyte apoptosis, and delineated the signal transduction mechanism in rats subjected to surgical trauma. Methods: Rats were randomized into two groups: control and trauma groups, which was divided into five subgroups: posttraumatic 0, 3, 6, 12, and 24 h subgroups. Cardiomyocytes isolated from traumatized rats were incubated with one of the factors for 12 h (normal plasma; Cytomix; TNF-α; IL-1β; IFN-γ; trauma plasma; anti-TNF-α antibody; SB203580). Myocyte apoptosis, cytokine levels, and MAPKs activation, as the primary experimental outcomes, were measured by TUNEL, flow cytometry, ELISA and Western blot, respectively. Results: Myocyte apoptosis was induced by surgical trauma during the early stage after trauma. Accompanying this change, plasma TNF-α, IL-1β, and IFN-γ levels were elevated in traumatized rats. Incubation of traumatized cardiomyocytes with cytomix or TNF-α alone induced myocyte apoptosis, and increased the activation of p38 and ERK1/2. Myocyte apoptosis and p38 activation were elevated in traumatized cardiomyocytes with trauma plasma, and these increases were partly abolished by anti-TNF-α antibody or SB203580. Conclusion: Our study demonstrated that there exists the TNF-α-mediated-p38-dependent signaling pathway that contributed to posttraumatic myocyte apoptosis of rats undergoing surgical trauma.

scholarly journals Roles of C-Repeat Binding Factors-Dependent Signaling Pathway in Jasmonates-Mediated Improvement of Chilling Tolerance of Postharvest Horticultural Commodities

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Libin Wang ◽  
Xiuxiu Sun ◽  
Weiqi Luo ◽  
Chunlu Qian
Keyword(s):  
Signal Transduction ◽  
Low Temperature ◽  
Signaling Pathway ◽  
Temperature Stress ◽  
Chilling Injury ◽  
Chilling Tolerance ◽  
Low Temperature Stress ◽  
Signal Molecules ◽  
Biotic Stresses ◽  
Dependent Signaling Pathway

C-repeat binding factor- (CBF-) dependent signaling pathway is proposed to be a key responder to low temperature stress in plant. Jasmonates (JAs), the endogenous signal molecules in plant, participate in plant defense against (a)biotic stresses; however, the mechanism has not been fully clarified so far. With the progress made in JAs biopathway, signal transduction, and their relationship with CBF-dependent signaling pathway, our knowledge of the roles of the CBF-dependent signaling pathway in JAs-mediated improvement of chilling tolerance accumulates. In this review, we firstly briefly review the chilling injury (CI) characteristics of postharvest horticultural commodities, then introduce the biopathway and signal transduction of JAs, subsequently summarize the roles of the CBF-dependent signaling pathway under low temperature stress, and finally describe the linkage between JAs signal transduction and the CBF-dependent signaling pathway.

scholarly journals Qingxuan Jiangya Decoction Mitigates Renal Interstitial Fibrosis in Spontaneously Hypertensive Rats by Regulating Transforming Growth Factor-β1/Smad Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Wangyu Liu ◽  
Shan Lin ◽  
Qiaoyan Cai ◽  
Ling Zhang ◽  
Aling Shen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Signaling Pathway ◽  
Spontaneously Hypertensive Rats ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Hypertensive Rats ◽  
Renal Interstitial Fibrosis ◽  
Spontaneously Hypertensive ◽  
Smad Signaling ◽  
Smad Signaling Pathway

Qingxuan Jiangya Decoction (QXJYD) is a traditional Chinese medicine commonly used in the clinical treatment of hypertension. Earlier studies had shown that QXJYD could inhibit the elevation of blood pressure in spontaneously hypertensive rats (SHRs) and prevent remodeling of arterial vessels. This study examines the therapeutic efficacy of QXJYD against elevated blood pressure using the SHR model, as well as the mechanisms behind its antihypertensive activity and protection against renal fibrosis. The results showed that QXJYD significantly attenuated the increase in blood pressure in SHRs and mitigated the development of renal interstitial fibrosis. In addition, QXJYD also robustly decreased the excess accumulation of extracellular matrix and attenuated the elevated expression of MMPs. The antihypertensive effects and renal protection of QXJYD were determined to be strongly associated with inhibition of TGF-β1/Smad signaling pathway.

scholarly journals mTOR inhibitor improves testosterone-induced myocardial hypertrophy in hypertensive rats

2021 ◽  
Author(s):  
Jianshu Chen ◽  
Jing Yu ◽  
Ruowen Yuan ◽  
Ningyin Li ◽  
Caie Li ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
Postmenopausal Women ◽  
Signaling Pathway ◽  
Mtor Inhibitor ◽  
Myocardial Hypertrophy ◽  
The Other ◽  
Female Rats ◽  
Myocardial Tissue ◽  
Hypertensive Rats

Compelling evidence have described the incidence of hypertension and left ventricular hypertrophy (LVH) in postmenopausal women is significantly increased worldwide. Our team’s previous research identified that androgen was an underlying factor contributing to increased blood pressure and LVH in postmenopausal women. However, little is known about how androgens affect LVH in postmenopausal hypertensive women. The purpose of this study was to evaluate the role of mTOR signaling pathway in myocardial hypertrophy in androgen-induced postmenopausal hypertension and whether mTOR inhibitors can protect the myocardium from androgen-induced interference to prevent and treat cardiac hypertrophy. For that, ovariectomized (OVX) spontaneously hypertensive rats (SHR) aged 12 weeks were used to study the effects of testosterone (T 2.85 mg/kg/weekly im) on blood pressure and myocardial tissue. On the basis of antihypertensive therapy (chlorthalidone 8mg/kg/day ig), the improvement of blood pressure and myocardial hypertrophy in rats treated with different dose gradients of rapamycin (0.8mg/kg/day Vs 1.5mg/kg/day Vs 2mg/kg/day ip) in OVX+ estrogens(E 9.6 mg/Kg/day, ig)+T group was further evaluated. After T intervention, the OVX female rats exhibited significant increments in the heart weight / tibial length (TL), area of cardiomyocytes and the mRNA expressions of atrial natriuretic peptide, β- myosin heavy chain and matrix metalloproteinase 9 accompanied by a significant reduction in the uterine weight/TL and issue inhibitor of metalloproteinase 1. Mammalian rapamycin receptor (mTOR), ribosomal protein S6 kinase (S6K1),4E-bindiong protein 1(4EBP1) and eukaryotic translation initiation factor 4E in myocardial tissue of OVX+E+T group were expressed at higher levels than those of the other four groups. On the other hand, rapamycin abolished the effects of T-induced cardiac hypertrophy, decreased the systolic and diastolic blood pressure of SHR, and inhibited the activation of mTOR/ S6K1/4EBP1 signaling pathway in a concentration-dependent manner. Collectively, these data suggest that the mTOR/S6K1/4EBP1 pathway is an important therapeutic target for the prevention of LVH in postmenopausal hypertensive female rats with high T levels. Our findings also support the standpoint that the mTOR inhibitor, rapamycin, can eliminate T-induced cardiomyocyte hypertrophy

Serum 25-hydroxyvitamin D is associated with renal fi brosis (experimental study)

2019 ◽  
Vol 23 (6) ◽  
pp. 100-107
Author(s):  
E. O. Bogdanova ◽  
G. T. Ivanova ◽  
O. V. Galkina ◽  
I. M. Zubina ◽  
O. N. Beresneva ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Renal Fibrosis ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Hydroxyvitamin D ◽  
Period 2

INTRODUCTION. Vitamin D deficiency is commonly observed in patients with chronic kidney disease (CKD) due to decreased biosynthesis of 1,25(OH)2D3 in damaged renal tubules and increased catabolism of 1,25(OH)2D3 and 25OHD3. There is a growing evidence that vitamin D deficiency may contribute to impaired kidney function. Interventional studies have shown that vitamin D and its analogs attenuate the progression of renal fibrosis in experiment, and reduce proteinuria in patients with CKD. The renoprotective effects of vitamin D go far beyond its classical role in maintaining bone and mineral metabolism, which is a result of its pleiotropic action. THE AIM: to investigate the association between 25OH-hydroxyvitamin D (25OHD) level and renal fibrosis in spontaneously hypertensive rats (SHR) with early stages of experimental CKD.MATERIAL AND METHODS. Systolic blood pressure (BP), proteinuria, albuminuria, creatinine (Cr), urea (Ur), inorganic phosphate (Pi), 25OHD in serum were measured in nephrectomized (NE) and sham operated (SO) spontaneously hypertensive rats SHR (follow-up period 2, 4 and 6 months) and SO Wistar Kyoto rats (follow-up period 2 months), morphological light-optical study of kidney tissue was performed.RESULTS. The experimental model corresponded to the initial stages of CKD (Ur: 6.64 – 13.36 mmol/L). A significant increase in the area of renal fibrosis in animals with NE correlated with an increase in blood pressure (r = 0.51, p <0.001), serum Cr (r = 0.76, p <0.001), and albuminuria (r = 0.64, p <0.001) and proteinuria (r = 0.78, p <0.001) and a decrease in the concentration of 25OHD in serum (r = -0.67, p <0.001). In multiple regression analyzes, a reliable association of fibrosis with 25OHD was maintained (β = -0.28, p = 0.012). In addition, in ROC-analysis the largest value of the area under the curve was obtained for 25OHD (AUC = 0.95) to detect interstitial fibrosis more than 10 %.CONCLUSION. 25OHD depression at the initial stages of experimental CKD and hypertension is independently associated with the development of renal fibrosis.

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