Anti-fibrotic impact of Carvedilol in a CCl-4 model of liver fibrosis via serum microRNA-200a/SMAD7 enhancement to bridle TGF-β1/EMT track

El-Wakeel, Sara A.; Rahmo, Rania M.; El‐Abhar, Hanan S.

doi:10.1038/s41598-018-32309-1

Cited by 29 publications

(12 citation statements)

References 49 publications

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“…The results also showed that PD treatment reversed MP infection‐induced caspase‐3 expression (Figure A). Meanwhile, PD treatment reversed MP infection‐induced upregulation of the pro‐fibrosis‐related proteins α‐SMA, collagen I, and collagen III by suppression of TGF‐β expression (Figure A,E‐H), as reported previously . Together, these results suggest that PD treatment suppressed MP‐induced inflammation and fibrosis‐mediated lung injury by inhibiting activation of the NLRP3 inflammasome and NF‐κB pathway.…”

Section: Resultsmentioning

confidence: 99%

Polydatin suppresses the development of lung inflammation and fibrosis by inhibiting activation of the NACHT domain‐, leucine‐rich repeat‐, and pyd‐containing protein 3 inflammasome and the nuclear factor‐κB pathway after Mycoplasma pneumoniae infection

Tang

Wang

et al. 2018

J of Cellular Biochemistry

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Mycoplasma pneumoniae (MP) can infect both the upper and lower respiratory tracts. Polydatin (PD), a traditional Chinese medicine, is known to have anti-inflammation and antifibrosis properties. However, the protective effects of PD against MP pneumonia (MPP) remain unclear. So, the aim of this study was to describe the therapeutic effects and underlying mechanisms of PD against MPP. BALB/c mice were assigned to three groups: a normal control group, MP infection group, or PD-treated MP infection group. BEAS-2B cells transfected with or without NACHT domain-, leucine-rich repeat-, and pyd-containing protein 3 (NLRP3) were used to confirm the protective mechanisms of PD. Immunohistochemical analysis, Western blot analysis, enzyme-linked immunosorbent assay, and flow cytometry were used in this study. The results showed that PD treatment suppressed MP-induced lung injury in mice by suppressing the expression of inflammatory factors and inhibiting the development of pulmonary fibrosis. Meanwhile, PD treatment inhibited activation of the NLRP3 inflammasome and nuclear factor κB (NF-κB) pathway. Overexpression of NLRP3 reversed the protective effect of PD against MPinduced injury of BEAS-2B cells. Taken together, these results indicate that PD treatment suppressed the inflammatory response and the development of pulmonary fibrosis by inhibiting the NLRP3 inflammasome and NF-κB pathway after MP infection. K E Y W O R D S fibrosis, inflammation, Mycoplasma pneumoniae, NACHT domain-, leucine-rich repeat-, and pyd-containing protein 3, polydatin

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Section: Resultsmentioning

confidence: 99%

Polydatin suppresses the development of lung inflammation and fibrosis by inhibiting activation of the NACHT domain‐, leucine‐rich repeat‐, and pyd‐containing protein 3 inflammasome and the nuclear factor‐κB pathway after Mycoplasma pneumoniae infection

Tang

Wang

et al. 2018

J of Cellular Biochemistry

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“…Anti-fibrotic miRNAs which are known to be in involved in the regulation of EMT and are regulated in CCl 4 rat model such as members of the miR-200 family were not deregulated after treatment in our experiment. In a previous report, it was shown that CCl 4 mediated inhibition of miR-200a was enhanced after treatment with carvedilol [ 61 ]. Another important anti-fibrotic miRNA is represented by members of the miR-29 family.…”

Section: Discussionmentioning

confidence: 99%

Exosomal miRNAs as Potential Biomarkers to Monitor Phosphodiesterase 5 Inhibitor Induced Anti-Fibrotic Effects on CCl4 Treated Rats

Broermann

Schmid

Gabrielyan

et al. 2020

IJMS

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MicroRNAs (miRNAs) are short, non-coding RNA species that are important post-transcriptional regulators of gene expression and play an important role in the pathogenesis of non-alcoholic fatty liver disease. Here, we investigated the phosphodiesterase 5 (PDE5) inhibitor induced effects on hepatic and plasma exosomal miRNA expression in CCl4-treated rats. In the present study, hepatic miRNA profiling was conducted using the Nanostring nCounter technology and mRNA profiling using RNA sequencing from PDE5 treated rats in the model of CCl4-induced liver fibrosis. To evaluate if the PDE5 inhibitor affected differentially expressed miRNAs in the liver can be detected in plasma exosomes, qRT-PCR specific assays were used. In livers from CCl4-treated rats, the expression of 22 miRNAs was significantly increased (>1.5-fold, adj. p < 0.05), whereas the expression of 16 miRNAs was significantly decreased (>1.5-fold, adj. p < 0.05). The majority of the deregulated miRNA species are implicated in fibrotic and inflammatory processes. The PDE5 inhibitor suppressed the induction of pro-fibrotic miRNAs, such as miR-99b miR-100 and miR-199a-5p, and restored levels of anti-fibrotic miR-122 and miR-192 in the liver. In plasma exosomes, we observed elevated levels of miR-99b, miR-100 and miR-142-3p after treatment with the PDE5-inhibitor compared to CCl4/Vehicle-treated. Our study demonstrated for the first time that during the development of hepatic fibrosis in the preclinical model of CCl4-induced liver fibrosis, defined aspects of miRNA regulated liver pathogenesis are influenced by PDE5 treatment. In conclusion, miRNA profiling of plasma exosomes might be used as a biomarker for NASH progression and monitoring of treatment effects.

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“…In this process, epithelial cells initiate the reprogramming of gene expression, which is manifested by a decrease in epithelial surface marker E-cadherin and increase in fibroblast surface marker α-SMA. In a rat model of renal fibrosis, El-Wakeel et al (33) demonstrated that the expression of E-cadherin decreased and the expression of α-SMA increased significantly. Similar results were also obtained in rat models of natural aging-associated renal fibrosis and of ureteral occlusion renal fibrosis (34,35).…”

Section: Discussionmentioning

confidence: 99%

Incremental load training improves renal fibrosis by regulating the TGF‑β1/TAK1/MKK3/p38MAPK signaling pathway and inducing the activation of autophagy in aged mice

Bao

Cai

et al. 2019

Int J Mol Med

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Recent studies have confirmed that kidney tissue fibrosis is closely linked to the natural aging of organs. One of its major characteristics is the reduction of autophagic activity. However, to date, few studies have assessed whether incremental load training is able to improve the occurrence of renal fibrosis caused by natural aging and the underlying mechanisms. In the present study involving male C57/BL mice, an elderly exercise group (OY group) was subjected to progressive load-increasing rotary-bar training (5 days/week, lasting for 6 weeks), with an elderly control group (OC group) and a young control group (YC group) used as controls. Renal fibrosis and autophagy-associated indicators were assessed by Masson's staining, reverse transcription-quantitative PCR analysis, western blotting, immunofluorescence and transmission electron microscopy. The results suggested that collagen deposition in the basal part of the renal tubular epithelium and glomeruli in the OY group was significantly lower than that in the OC group. In the OC group, the protein expression levels of E-cadherin, Beclin 1 and light chain 3 were significantly decreased, and increases in α-smooth muscle actin-positive signals were observed in the glomerular matrix and renal capsule wall. Furthermore, the expression of transforming growth factor (TGF)-β1 and its downstream signaling molecules TGF-β-activated kinase 1 (TAK1), mitogen-activated protein kinase (MAPK) kinase (MKK3) and p38MAPK were downregulated following training. The present study confirmed that incremental load training may improve renal fibrosis in aged mice by regulating the TGF-β1/TAK1/MMK3/p38MAPK signaling pathway and inducing the activation of autophagy to reduce the synthesis of extracellular matrix and delay the epithelial-mesenchymal transition. The present study provides a novel experimental basis for the intervention of incremental load training to prevent senile renal fibrosis.

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Anti-fibrotic impact of Carvedilol in a CCl-4 model of liver fibrosis via serum microRNA-200a/SMAD7 enhancement to bridle TGF-β1/EMT track

Cited by 29 publications

References 49 publications

Polydatin suppresses the development of lung inflammation and fibrosis by inhibiting activation of the NACHT domain‐, leucine‐rich repeat‐, and pyd‐containing protein 3 inflammasome and the nuclear factor‐κB pathway after Mycoplasma pneumoniae infection

Polydatin suppresses the development of lung inflammation and fibrosis by inhibiting activation of the NACHT domain‐, leucine‐rich repeat‐, and pyd‐containing protein 3 inflammasome and the nuclear factor‐κB pathway after Mycoplasma pneumoniae infection

Exosomal miRNAs as Potential Biomarkers to Monitor Phosphodiesterase 5 Inhibitor Induced Anti-Fibrotic Effects on CCl4 Treated Rats

Incremental load training improves renal fibrosis by regulating the TGF‑β1/TAK1/MKK3/p38MAPK signaling pathway and inducing the activation of autophagy in aged mice

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