Targeting the Wnt/β-Catenin Signaling Pathway as a Potential Therapeutic Strategy in Renal Tubulointerstitial Fibrosis

Li, Shanshan; Sun, Qian; Hua, Meng-Ru; Suo, Ping; Chen, Jia‐Rong; Yu, Xiao; Yan, Zhao

doi:10.3389/fphar.2021.719880

Cited by 53 publications

(50 citation statements)

References 178 publications

(178 reference statements)

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“…In addition, E-cadherin and vimentin are considered the most important epithelial cell markers and mesenchymal cell phenotypic markers during EMT [ 34 ]. Many experiments have confirmed that the decrease of E-cadherin protein activity is the first step for tumor cells to acquire the ability of dedifferentiation and invasion [ 35 ], that is, E-cadherin protein can inhibit the invasion and migration of tumor cells [ 36 ]. Meanwhile, overexpression of vimentin can promote the invasion and migration of tumor cells [ 37 ], while blocking its expression through molecular biological methods can significantly reduce the invasion ability of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

[Retracted] Effect of FLOT2 Gene Expression on Invasion and Metastasis of Colorectal Cancer and Its Molecular Mechanism under Nanotechnology and RNA Interference

Zhong

Zheng

et al. 2022

BioMed Research International

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The study is aimed at investigating the effect of the FLOT2 gene on invasion and metastasis of colorectal cancer (CRC) cells and the corresponding molecular mechanism by preparing polylysine-silicon nanoparticles. Specifically, polylysine was used to modify the silica nanoparticles prepared by the emulsification method to obtain polylysine-silicon nanoparticles. The characterization of polylysine-silicon nanoparticles was completed by nanoparticle size analyzer, laser particle size potentiometer, and transmission microscope. The influence of polylysine-silicon nanoparticles on the survival rate of CRC cell line HT-29 was detected using the method of 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT). The FLOT2-siRNA expression vector was constructed and transfected with HT-29. The HT-29 transfected with empty plasmid was used as the negative control (NC). Western Blot (WB) and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect expression levels of FLOT2 gene and epithelial-mesenchymal transition- (EMT-) related genes. Transwell invasion assay, Transwell migration assay, and CCK8 assay were used to detect the cell invasion, migration, and proliferation. The results showed that the average particle size of polylysine-silicon nanoparticles was 30 nm, the potential was 19.65 mV, the particle size was 65.8 nm, and the dispersion coefficient was 0.103. At the same concentration, the toxicity of silicon nanoparticles to HT-29 was significantly lower than that of liposome reagent, and the transfection efficiency was 60%, higher than that of liposome reagent (40%). The mRNA level and protein expression of the FLOT2 gene in the FLOT2-siRNA group were significantly lower than those in the NC group ( P < 0.01 ). The optical density (OD) value of the NC group and the blank control (CK) group were significantly higher than that of FLOT2-siRNA cells ( P < 0.01 ). The OD value of FLOT2-siRNA cells was lower than that of NC cells at 48 h, 72 h, and 96 h ( P < 0.01 ). The mRNA levels and protein expressions of MMP2 and vimentin in the FLOT2-siRNA group were significantly lower than those in the NC group and CK group ( P < 0.01 ). The mRNA level and protein expression of the E-cadherin gene in the FLOT2-siRNA group were significantly higher than those in the NC group and CK group ( P < 0.01 ). In conclusion, an RNA interference plasmid with high transfection efficiency and low cytotoxicity was established based on nanotechnology. siRNA-mediated FLOT2 protein inhibits the invasion, migration, and proliferation of CRC cells by regulating the expression changes of EMT-related genes, which provides a scientific basis for clinical treatment of CRC.

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Section: Discussionmentioning

confidence: 99%

[Retracted] Effect of FLOT2 Gene Expression on Invasion and Metastasis of Colorectal Cancer and Its Molecular Mechanism under Nanotechnology and RNA Interference

Zhong

Zheng

et al. 2022

BioMed Research International

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“…Interestingly, the promoter region of the RAS gene also contains LEF/TCF binding sites, which allows β-catenin to promote the binding of LEF-1 to these sites [ 7 ]. Therefore, targeting the Wnt/β-catenin/RAS signaling pathway could be a potential therapeutic strategy for renal fibrosis [ 8 , 9 ]. In recent years, the replacement therapy of renal fibrosis by natural products has attracted the attention of many scholars [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Extract of Corallodiscus flabellata attenuates renal fibrosis in SAMP8 mice via the Wnt/β-catenin/RAS signaling pathway

Cao

Zeng

et al. 2022

BMC Complement Med Ther

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Background Fibrosis is one of the most common pathological features of the aging process of the kidney, and fibrosis in aging kidneys also aggravates the process of chronic kidney disease (CKD). Corallodiscus flabellata B. L. Burtt (C. flabellata, CF) is a commonly used botanical drug in Chinese folklore. However, few studies have reported its pharmacological effects. This study aimed to explore the effect of CF ethanol extract on renal fibrosis in SAMP8 mice and identify potentially active compounds. Methods Senescence-accelerated mouse-prone 8 (SAMP8) were used as animal models, and different doses of CF were given by gavage for one month. To observe the degree of renal aging in mice using β-galactosidase staining. Masson staining and the expression levels of Col-I, α-SMA, and FN were used to evaluate the renal fibrosis in mice. The protein expression levels of Nrf2 pathway and Wnt/β-catenin/RAS pathway in the kidney were measured. And β-galactosidase (β-gal) induced NRK-52E cells as an in vitro model to screen the active components of CF. Results The CF ethanol extract significantly inhibited the activity of renal β-galactosidase and the expression levels of Col-I, α-SMA, and FN in SAMP8 mice, and improved Masson staining in SAMP8 mice. CF remarkably reduced urinary protein, creatinine, urea nitrogen and serum levels of TNF-α and IL-1β in SAMP8 mice, and significantly increased the levels of SOD and GSH-Px. Moreover, CF activated the Nrf2 pathway and blocked the Wnt/β-catenin/RAS pathway in the kidneys of mice. Besides, 3,4-dihydroxyphenylethanol (SDC-0-14, 16) and (3,4-dihydroxyphenylethanol-8-O-[4-O-trans-caffeoyl-β-D-apiofuranosyl-(1→3)-β-D-glucopyranosyl (1→6)]-β-D-glucopyranoside (SDC-1-8) were isolated from CF, which reduced the senescence of NRK-52E cells, and maybe the active ingredients of CF playing the anti-aging role. Conclusions Our experiments illuminated that CF ethanol extract may ameliorate renal fibrosis in SAMP8 mice via the Wnt/β-catenin/RAS pathway. And SDC-0-14,16 and SDC-1-8 may be the material basis for CF to exert anti-renal senescence-related effects.

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“…The expression of E-cadherin protein could be preserved by the genetic ablation of MMP-7 and substantially reduced the expression of total and dephosphorylated β-catenin. Li et al (2021) reviewed that MMP-7 could activate the Wnt/β-catenin signaling pathway after renal injury and urinary MMP-7 may be a noninvasive biomarker of profibrotic signaling in the kidney. In contrast, they discovered that MMP-7 exerts protective effects on the kidney as an adaptive response in cisplatin administration or folic acid-induced AKI animal models.…”

Section: Mmpsmentioning

confidence: 99%

Advances in the Progression and Prognosis Biomarkers of Chronic Kidney Disease

Yan¹,

Wang²,

Shi³

2021

Front. Pharmacol.

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Chronic kidney disease (CKD) is one of the increasingly serious public health concerns worldwide; the global burden of CKD is increasingly due to high morbidity and mortality. At present, there are three key problems in the clinical treatment and management of CKD. First, the current diagnostic indicators, such as proteinuria and serum creatinine, are greatly interfered by the physiological conditions of patients, and the changes in the indicator level are not synchronized with renal damage. Second, the established diagnosis of suspected CKD still depends on biopsy, which is not suitable for contraindication patients, is also traumatic, and is not sensitive to early progression. Finally, the prognosis of CKD is affected by many factors; hence, it is ineviatble to develop effective biomarkers to predict CKD prognosis and improve the prognosis through early intervention. Accurate progression monitoring and prognosis improvement of CKD are extremely significant for improving the clinical treatment and management of CKD and reducing the social burden. Therefore, biomarkers reported in recent years, which could play important roles in accurate progression monitoring and prognosis improvement of CKD, were concluded and highlighted in this review article that aims to provide a reference for both the construction of CKD precision therapy system and the pharmaceutical research and development.

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Targeting the Wnt/β-Catenin Signaling Pathway as a Potential Therapeutic Strategy in Renal Tubulointerstitial Fibrosis

Cited by 53 publications

References 178 publications

[Retracted] Effect of FLOT2 Gene Expression on Invasion and Metastasis of Colorectal Cancer and Its Molecular Mechanism under Nanotechnology and RNA Interference

[Retracted] Effect of FLOT2 Gene Expression on Invasion and Metastasis of Colorectal Cancer and Its Molecular Mechanism under Nanotechnology and RNA Interference

Extract of Corallodiscus flabellata attenuates renal fibrosis in SAMP8 mice via the Wnt/β-catenin/RAS signaling pathway

Advances in the Progression and Prognosis Biomarkers of Chronic Kidney Disease

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