Nootkatone confers antifibrotic effect by regulating the TGF-β/Smad signaling pathway in mouse model of unilateral ureteral obstruction

2021 ◽  
pp. 174479
Author(s):  
Shobhit Gairola ◽  
Chetan Ram ◽  
Abu Mohammad Syed ◽  
Pakpi Doye ◽  
Uttam Kulhari ◽  
...  
Keyword(s):  
Mouse Model ◽  
Signaling Pathway ◽  
Ureteral Obstruction ◽  
Unilateral Ureteral Obstruction ◽  
Smad Signaling ◽  
Antifibrotic Effect ◽  
Smad Signaling Pathway

scholarly journals Sirtuin 3 Activation by Honokiol Decreases Unilateral Ureteral Obstruction-Induced Renal Inflammation and Fibrosis via Regulation of Mitochondrial Dynamics and the Renal NF-κB-TGF-β1/Smad Signaling Pathway

2020 ◽  
Vol 21 (2) ◽  
pp. 402 ◽  
Author(s):  
Yi Quan ◽  
Woong Park ◽  
Jixiu Jin ◽  
Won Kim ◽  
Sung Kwang Park ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Mitochondrial Dynamics ◽  
Unilateral Ureteral Obstruction ◽  
Sirtuin 3 ◽  
Smad Signaling ◽  
Renal Tubulointerstitial Fibrosis ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Renal fibrosis is a common feature of all progressive chronic kidney diseases. Sirtuin 3 (SIRT3) is one of the mitochondrial sirtuins, and plays a role in the regulation of mitochondrial biogenesis, oxidative stress, fatty acid metabolism, and aging. Recently, honokiol (HKL), as a pharmaceutical SIRT3 activator, has been observed to have a protective effect against pressure overload-induced cardiac hypertrophy by increasing SIRT3 activity. In this study, we investigated whether HKL, as a SIRT3 activator, also has protective effects against unilateral ureteral obstruction (UUO)-induced renal tubulointerstitial fibrosis through SIRT3-dependent regulation of mitochondrial dynamics and the nuclear factor-κB (NF-κB)/transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. We found that HKL decreased the UUO-induced increase in tubular injury and extracellular matrix (ECM) deposition in mice. HKL also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells. Finally, we showed that HKL treatment decreased UUO-induced mitochondrial fission and promoted mitochondrial fusion through SIRT3-dependent effects. In conclusion, activation of SIRT3 via HKL treatment might have beneficial effects on UUO-induced renal fibrosis through SIRT3-dependent regulation of mitochondrial dynamics and the NF-κB/TGF-β1/Smad signaling pathway.

scholarly journals HuangQi Decoction Ameliorates Renal Fibrosis via TGF-β/Smad Signaling Pathway In Vivo and In Vitro

2016 ◽  
Vol 38 (5) ◽  
pp. 1761-1774 ◽  
Author(s):  
Jie Zhao ◽  
Li Wang ◽  
Ai-li Cao ◽  
Ming-Qian Jiang ◽  
Xia Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ureteral Obstruction ◽  
Interstitial Fibrosis ◽  
Unilateral Ureteral Obstruction ◽  
Type I ◽  
Renal Interstitial Fibrosis ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Tgf Β1

Objective: Traditional Chinese Medicine compound HuangQi decoction is widely used in clinical treatment of chronic kidney disease, but its role on renal interstitial fibrosis and the underlying mechanism remains unclear. The aim of this study is to investigate the effect of HuangQi decoction on renal interstitial fibrosis and its association with the TGF-β/Smad signaling pathway Methods: A total of 120 C57/BL mice were randomly divided into six groups: sham group, sham plus high-dose HuangQi decoction (1.08g/kg) group, unilateral ureteral obstruction (UUO) model group, and UUO model plus low to high doses of HuangQi decoction (0.12g/kg, 0.36g/kg and 1.08g/kg respectively) groups. Animals were sacrificed 14 days after the administration and ipsilateral kidney tissue was sampled for pathologic examinations. Immunohistochemistry, PCR and western blot were used to detect the expressions of related molecules in the TGF-β/Smad signaling pathway. TGF-β1 was used in in vitro experiments to induce human kidney proximal tubule epithelial cells (HK2). Results: HuangQi decoction improved ipsilateral kidney fibrosis in UUO mice and downregulated the expressions of TGF-β1, TβRI, TβRII, Smad4, Smad2/3, P-Smad2/3, α-SMA, collagen type I, III and IV in a dose-dependent manner while upregulated the expression of Smad7 in the same fashion. Similar results were found in in vitro studies. Conclusion: The protective effect of HuangQi decoction for unilateral ureteral obstruction kidney damage in mice was mediated by downregulating the TGF-β/Smad signaling pathway.

scholarly journals Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and Fibrosis

2020 ◽  
Vol 21 (21) ◽  
pp. 8184
Author(s):  
Jixiu Jin ◽  
Tian Wang ◽  
Woong Park ◽  
Wenjia Li ◽  
Won Kim ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ureteral Obstruction ◽  
Transforming Growth Factor ◽  
Unilateral Ureteral Obstruction ◽  
Age Related Macular Degeneration ◽  
Smad Signaling ◽  
Matrix Deposition ◽  
Smad Signaling Pathway ◽  
Tgf Β1 ◽  
Tubulointerstitial Inflammation

Yes-associated protein (YAP) activation after acute ischemic kidney injury might be related to interstitial fibrosis and impaired renal tubular regeneration. Verteporfin (VP) is a photosensitizer used in photodynamic therapy to treat age-related macular degeneration. In cancer cells, VP inhibits TEA domain family member (TEAD)-YAP interactions without light stimulation. The protective role of VP in unilateral ureteral obstruction (UUO)-induced renal fibrosis and related mechanisms remains unclear. In this study, we investigate the protective effects of VP on UUO-induced renal tubulointerstitial inflammation and fibrosis and its regulation of the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. We find that VP decreased the UUO-induced increase in tubular injury, inflammation, and extracellular matrix deposition in mice. VP also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells by modulating Smad2 and Smad3 phosphorylation. Therefore, YAP inhibition might have beneficial effects on UUO-induced tubulointerstitial inflammation and fibrosis by regulating the TGF-β1/Smad signaling pathway.

scholarly journals The BMP4-Smad signaling pathway regulates hyperandrogenism development in a female mouse model

2017 ◽  
Vol 292 (28) ◽  
pp. 11740-11750 ◽  
Author(s):  
Yang Liu ◽  
Shao-Yue Du ◽  
Meng Ding ◽  
Xin Dou ◽  
Fei-Fei Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Signaling Pathway ◽  
Female Mouse ◽  
Smad Signaling ◽  
Smad Signaling Pathway

scholarly journals microRNA-590-3p regulates inflammation and organ dysfunction in sepsis mouse model via the Syap1-mediated TGF-β/Smad signaling pathway

2021 ◽  
Author(s):  
Yiming Li ◽  
Yanjing Huang ◽  
Zhihong Lin ◽  
Xiaofeng Huang
Keyword(s):  
Mouse Model ◽  
Signaling Pathway ◽  
Organ Dysfunction ◽  
Inflammatory Cytokines ◽  
Cell Apoptosis ◽  
Luciferase Reporter ◽  
Organ Function ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Liver Tissues

Abstract Sepsis is a common cause of death among patients in intensive care unit. Recent evidence indicates that microRNAs (miRs) might serve as potential biomarkers facilitating an early diagnosis of sepsis. Herein, we aimed to examine the mechanisms by which miR-590-3p may regulate inflammatory response and organ dysfunction during sepsis progression. The Gene Expression Omnibus (GEO) database was used to identify differentially expressed genes in an established sepsis mouse model, and the related miRNAs and downstream regulatory pathways were predicted using web-available microarrays. A sepsis animal model was induced in mice by cecal ligation and puncture (CLP). Indices of cardiac function, serum myocardial enzymes, and organ function were measured to confirm successful generation of the sepsis mouse model. Cell apoptosis and inflammatory cytokine levels in lung and liver tissues were observed by TUNEL staining and ELISA. Furthermore, the interaction between miR-590-3p and Synapse-associated protein 1 (Syap1) was identified by dual luciferase reporter gene assay. The effect of miR-590-3p on inflammation and organ dysfunction was examined using gain- and loss-of-function experiments. Syap1 was found poorly expressed, whereas miR-590-3p was highly expressed in the sepsis-affected mice. Moreover, the elevation of miR-590-3p markedly downregulated the expression of anti-inflammatory cytokines IL10, Syap1, TGF-β, Smad3, and NF-кB p65 in modeled mice. Indices of cardiac and organ function were decreased, serum myocardial enzyme indices were notably increased, and cell apoptosis and pro-inflammatory cytokines of lung and liver tissues were increased in modeled mice. Together these results demonstrated that miR-590-3p can block the TGF-β/Smad signaling pathway through downregulation of Syap1 and, thereby, contribute to sepsis inflammation and organ dysfunction.

A natural product of acteoside ameliorate kidney injury in diabetes db/db mice and HK ‐2 cells via regulating NADPH / oxidase‐TGF ‐β/Smad signaling pathway

2021 ◽  
Author(s):  
Qinwen Wang ◽  
Xinxin Dai ◽  
Xiang Xiang ◽  
Zhuo Xu ◽  
Shulan Su ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Natural Product ◽  
Signaling Pathway ◽  
Kidney Injury ◽  
Smad Signaling ◽  
Smad Signaling Pathway
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