Dataset Information

Emodin Retarded Renal Fibrosis Through Regulating HGF and TGF?-Smad Signaling Pathway.

ABSTRACT: Background:Renal fibrosis is a frequently occurring type of chronic kidney disease that can cause end-stage renal disease. It has been verified that emodin or HGF can inhibit the development of renal fibrosis. However, the antifibrotic effect of emodin in combination with HGF remains unclear. Methods:Cell viability was detected with CCK8. Gene and protein expression in HK2 cells was detected by qRT-PCR and Western blot, respectively. Moreover, a unilateral ureteral obstruction-induced mouse model of renal fibrosis was established for investigating the antifibrotic effect of emodin in combination with HGF in vivo. Results:HGF notably increased the expression of collagen II in TGF?-treated HK2 cells. In addition, HGF-induced increase in collagen II expression was further enhanced by emodin. In contrast, fibronectin, ?SMA and Smad2 expression in TGF?-stimulated HK2 cells was significantly inhibited by HGF and further decreased by combination treatment (emodin plus HGF). Moreover, we found that combination treatment exhibited better antifibrotic effects compared with emodin or HGF in vivo. Conclusion:These data demonstrated that emodin plus HGF exhibited better antifibrotic effects compared with emodin or HGF. As such, emodin in combination with HGF may serve as a new possibilty for treatment of renal fibrosis.

SUBMITTER: Yang F

PROVIDER: S-EPMC7478377 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Emodin Retarded Renal Fibrosis Through Regulating HGF and TGFβ-Smad Signaling Pathway.

Yang Fan F Deng Lu L Li JinPeng J Chen MuHu M Liu Ying Y Hu YingChun Y Zhong Wu W

Drug design, development and therapy 20200903

<h4>Background</h4>Renal fibrosis is a frequently occurring type of chronic kidney disease that can cause end-stage renal disease. It has been verified that emodin or HGF can inhibit the development of renal fibrosis. However, the antifibrotic effect of emodin in combination with HGF remains unclear.<h4>Methods</h4>Cell viability was detected with CCK8. Gene and protein expression in HK2 cells was detected by qRT-PCR and Western blot, respectively. Moreover, a unilateral ureteral obstruction-ind ...[more]

PMID: 32943844

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Project description:Renal fibrosis denotes a common complication of diabetic nephropathy and is a predominant cause of end-stage renal disease. Despite the association between microRNAs (miRNAs or miRs) and renal fibrosis, miRNAs have been reported to play a vital role in the development of chronic renal fibrosis. Therefore, the aim of the present study was to investigate the possible function of miR-101a in chronic renal fibrosis. Initially, microarray-based gene expression profiling of renal fibrosis was employed to screen the differentially expressed genes. An in vivo mouse model of chronic renal fibrosis induced by a unilateral ureteral obstruction (UUO) and an in vitro cell model induced by aristolochic acid (AA) were constructed. miR-101a expression was examined using a fluorescence in situ hybridization (FISH) assay and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Then, the interaction between miR-101a and KDM3A was identified using an online website combined with a dual-luciferase reporter assay. Finally, gain- and loss-of-function experiments were conducted to elucidate the effect of miR-101a on the expression of Col1a1, fibronectin, ?-smooth muscle actin (?-SMA), and YAP-TGF-? (transforming growth factor ?)-Smad signaling pathway-related genes, as well as the degree of renal fibrosis. miR-101a was poorly expressed while KDM3A was robustly induced in chronic renal fibrosis tissues and cells. In addition, miR-101a could target and downregulate KDM3A expression, which led to elevated TGIF1, inhibited expression of Collagen I (Col1a1), fibronectin, ?-SMA, YAP1, and TGF-?2 along with the extent of Smad2/3 phosphorylation, as well as delayed renal fibrosis degree. Besides, overexpressed YAP/TGF-?2 or inhibited TGIF1 partially restored the inhibitory effect of miR-101a on chronic renal fibrosis. Taken together, miR-101a could potentially slow down chronic renal fibrosis by the inactivation of the YAP-TGF-?-Smad signaling pathway via KDM3A, highlighting the potential of miR-101a as a therapeutic target for chronic renal fibrosis treatment.

Project description:PurposePathological fibrosis of the myodural bridge (MDB) affects cerebrospinal fluid circulation. However, no optimal drug treatments are available. We aimed to explore the antifibrotic effect of resveratrol on bleomycin-induced pathological fibrosis of the MDB and its underlying mechanisms.MethodsGenes common to the potential targets of resveratrol were determined using network pharmacology, genes related to muscle and tendon fibrosis were acquired from the GeneCards database, and genes related to MDB development were determined using Venny. These genes were considered potential resveratrol treatment targets in bleomycin-induced pathological fibrosis of the MDB and were annotated using bioinformatics methods. We validated the intersected genes using quantitative real-time polymerase chain reaction (qRT-PCR) and performed molecular docking analysis to calculate the binding activity between the target gene and resveratrol. Hematoxylin and eosin and Masson staining were used to detect the morphological changes in bleomycin-induced fibrosis of the MDB following resveratrol treatment. We used qRT-PCR and immunohistochemistry to evaluate the expression of the sirtuin 3 (SIRT3)/transforming growth factor-β1 (TGF-β1)/Smad pathway and the profibrotic markers α-smooth muscle actin (α-SMA) and Collagen Ⅰ.ResultsThrough network pharmacology and bioinformatics analyses, we identified four core intersected genes, and SIRT3 expression was validated using qRT-PCR. Molecular docking analysis revealed that resveratrol had good binding affinity for SIRT3. Resveratrol ameliorated morphological abnormalities in bleomycin-induced pathological fibrosis of the MDB by inhibiting fibroblast activation and excessive collagen fiber deposition. Resveratrol exerted its antifibrotic effect by regulating the SIRT3/TGF-β1/Smad pathway.ConclusionResveratrol has an antifibrotic effect in bleomycin-induced pathological fibrosis of the MDB in vivo and may be considered a novel therapeutic strategy.

Dataset Information

Emodin Retarded Renal Fibrosis Through Regulating HGF and TGF?-Smad Signaling Pathway.

Publications

Emodin Retarded Renal Fibrosis Through Regulating HGF and TGFβ-Smad Signaling Pathway.

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