Cardiac Contractility Modulation Attenuate Myocardial Fibrosis by Inhibiting TGF-β1/Smad3 Signaling Pathway in a Rabbit Model of Chronic Heart Failure

Zhang, Feifei; Dang, Yi; Li, Yingxiao; Hao, Qian; Li, Rong; Qi, Xiaodan

doi:10.1159/000445624

Cited by 45 publications

(41 citation statements)

References 29 publications

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“…TGF‐β1/Smad pathway contributes to ECM formation by disturbing MMPs/TIMPs balance . TGF‐β1 stimulates MMP9 protein expression through Smad‐dependent pathway in rabbit myocardial fibrosis model and HepG2 cells . TGF‐β1 up‐regulates the protein levels of MMP9 and TIMP1 and further induces ECM accumulation in diethylnitrosamine‐induced hepatic fibrosis in rats .…”

Section: Discussionmentioning

confidence: 99%

“…65 TGF-β1 stimulates MMP9 protein expression through Smad-dependent pathway in rabbit myocardial fibrosis model and HepG2 cells. 56,66 TGF-β1 up-regulates the protein levels of MMP9 and TIMP1 and further induces ECM accumulation in diethylnitrosamineinduced hepatic fibrosis in rats. 67 In addition, SB431542 suppresses the TGF-β1-induced TIMP1 overproduction in human dental pulp cells.…”

Section: Tgf-β1/smad Pathway Contributes To Ecm Formation By Disturbingmentioning

confidence: 99%

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TGF‐β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro

Zhang

Chang

Wang

et al. 2019

Environmental Toxicology

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Nickel oxide nanoparticles (Nano NiO) bears hepatotoxicity, while whether it leads to liver fibrosis remains unclear. The aim of this study was to establish the Nano NiO‐induced hepatic fibrosis model in vivo and investigate the roles of transforming growth factor β1 (TGF‐β1) in Smad pathway activation, epithelial‐mesenchymal transition (EMT) occurrence, and extracellular matrix (ECM) deposition in vitro. Male Wistar rats were exposed to 0.015, 0.06, and 0.24 mg/kg Nano NiO by intratracheal instilling twice a week for 9 weeks. HepG2 cells were treated with 100 μg/mL Nano NiO and TGF‐β1 inhibitor (SB431542) to explore the mechanism of collagen formation. Results of Masson staining as well as the elevated levels of type I collagen (Col‐I) and Col‐III suggested that Nano NiO resulted in hepatic fibrosis in rats. Furthermore, Nano NiO increased the protein expression of TGF‐β1, p‐Smad2, p‐Smad3, alpha‐smooth muscle actin (α‐SMA), matrix metalloproteinase9 (MMP9), and tissue inhibitors of metalloproteinase1 (TIMP1), while decreased the protein content of E‐cadherin and Smad7 in rat liver and HepG2 cells. Most importantly, Nano NiO‐triggered the abnormal expression of the abovementioned proteins were all alleviated by co‐treatment with SB431542, implying that TGF‐β1‐mediated Smad pathway, EMT and MMP9/TIMP1 imbalance were involved in overproduction of collagen in HepG2 cells. In conclusion, these findings indicated that Nano NiO induced hepatic fibrosis via TGF‐β1‐mediated Smad pathway activation, EMT occurrence, and ECM deposition.

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Section: Discussionmentioning

confidence: 99%

Section: Tgf-β1/smad Pathway Contributes To Ecm Formation By Disturbingmentioning

confidence: 99%

TGF‐β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro

Zhang

Chang

Wang

et al. 2019

Environmental Toxicology

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“…Excessive SGK1 expression was observed in lung fibrosis, diabetic nephropathy, glomerulonephritis, experimental nephrotic syndrome, obstructive nephropathy, liver cirrhosis, fibrosing pancreatitis, peritoneal fibrosis, Crohn´s disease and coeliac disease [7, 43, 91, 92]. SGK1 expression is up-regulated by TGFβ [43], a key stimulator of fibrosis [88, 93-98]. TGFß is in part effective through transcription factors Smad2/3 [7], which are degraded by the ubiquitin ligase Nedd4L [7].…”

Section: Sgk1 Sensitive Infammation and Fbrosismentioning

confidence: 99%

Two Liters a Day Keep the Doctor Away? Considerations on the Pathophysiology of Suboptimal Fluid Intake in the Common Population

Läng

Guelinckx

Lemetais

et al. 2017

Kidney Blood Press Res

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Suboptimal fluid intake may require enhanced release of antidiuretic hormone (ADH) or vasopressin for the maintenance of adequate hydration. Enhanced copeptin levels (reflecting enhanced vasopressin levels) in 25% of the common population are associated with enhanced risk of metabolic syndrome with abdominal obesity, type 2 diabetes, hypertension, coronary artery disease, heart failure, vascular dementia, cognitive impairment, microalbuminuria, chronic kidney disease, inflammatory bowel disease, cancer, and premature mortality. Vasopressin stimulates the release of glucocorticoids which in turn up-regulate the serum- and glucocorticoid-inducible kinase 1 (SGK1). Moreover, dehydration upregulates the transcription factor NFAT5, which in turn stimulates SGK1 expression. SGK1 is activated by insulin, growth factors and oxidative stress via phosphatidylinositide-3-kinase, 3-phosphoinositide-dependent kinase PDK1 and mTOR. SGK1 is a powerful stimulator of Na⁺/K⁺-ATPase, carriers (e.g. the Na⁺,K⁺,2Cl^- cotransporter NKCC, the NaCl cotransporter NCC, the Na⁺/H⁺ exchanger NHE3, and the Na⁺ coupled glucose transporter SGLT1), and ion channels (e.g. the epithelial Na⁺ channel ENaC, the Ca²⁺ release activated Ca²⁺ channel Orai1 with its stimulator STIM1, and diverse K⁺ channels). SGK1 further participates in the regulation of the transcription factors nuclear factor kappa-B NFκB, p53, cAMP responsive element binding protein (CREB), activator protein-1, and forkhead transcription factor FKHR-L1 (FOXO3a). Enhanced SGK1 activity fosters the development of hypertension, obesity, diabetes, thrombosis, stroke, inflammation including inflammatory bowel disease and autoimmune disease, cardiac fibrosis, proteinuria, renal failure as well as tumor growth. The present brief review makes the case that suboptimal fluid intake in the common population may enhance vasopressin and glucocorticoid levels thus up-regulating SGK1 expression and favouring the development of SGK1 related pathologies.

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“…However, this change was reversed by QSG treatment (P < 0.01, Figure 4). Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) are important for degradation of the extracellular matrix [29]. In this study, MMP-2 and MMP-9 levels in serum were significantly upregulated in the model group compared with the sham group (P < 0.01, Figure 4).…”

Section: Qsg Reduced Ald Piiinp Mmp-2 and Mmp-9mentioning

confidence: 55%

Antiapoptosis and Antifibrosis Effects of Qishen Granules on Heart Failure Rats via Hippo Pathway

Zhang

Liu

Gao

et al. 2019

BioMed Research International

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Qishen granules (QSG) are a famous formula with cardioprotective properties to heart failure (HF). The aim of this study was to investigate the underlying mechanism of QSG on apoptosis and fibrosis in the treatment of HF. HF model was induced by left anterior descending artery ligation on Sprague-Dawley rats. Transcriptome analysis was used to investigate the regulatory pathways of QSG on HF. Interestingly, downregulated genes of QSG were significantly enriched in Hippo pathway which plays a crucial role in regulating cell apoptosis and proliferation. We found that QSG inhibited the expressions of proapoptotic key proteins P-53 and fibrosis-related proteins TGF-β1, SMAD3, and CTGF. Further, we conducted research on the key proteins in the Hippo pathway upstream of CTGF and P-53. The results showed that MST1, P-MST1, P-LATS1, and RASSF1A that exert proapoptotic function were downregulated after QSG intervention. Similarly, P-YAP and P-TAZ, mediating self-degradation and apoptosis, were both observably decreased after QSG administration. Taken together, QSG are shown to be likely to exert cardioprotective effects by inhibiting the progression of apoptosis and fibrosis through Hippo pathway.

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Cardiac Contractility Modulation Attenuate Myocardial Fibrosis by Inhibiting TGF-β1/Smad3 Signaling Pathway in a Rabbit Model of Chronic Heart Failure

Cited by 45 publications

References 29 publications

TGF‐β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro

TGF‐β1 mediated Smad signaling pathway and EMT in hepatic fibrosis induced by Nano NiO in vivo and in vitro

Two Liters a Day Keep the Doctor Away? Considerations on the Pathophysiology of Suboptimal Fluid Intake in the Common Population

Antiapoptosis and Antifibrosis Effects of Qishen Granules on Heart Failure Rats via Hippo Pathway

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