Curcumin Interferes with TGF- β 1-Induced Fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation

Xu, Ben; Zhang, Jia-en; Ye, Lin; Yuan, Chang-wei

doi:10.1007/s11655-023-3564-9

Cited by 2 publications

(2 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At 2 weeks after birth, the kidney fully develops. Previous studies by our team confirmed the role of the ADAMTS18 gene in renal chronic fibrosis in an in vitro cell line [29] and confirmed the reversal of obstructive fibrosis via overexpression of the ADAMTS18 gene in a rat model with ureteral obstruction [30]. These findings fully indicate that ADAMTS18 is a stage-specific gene closely related to renal development.…”

Section: Discussionsupporting

confidence: 75%

The Role of the ADAMTS18 Gene-Induced Immune Microenvironment in Mouse Kidney Development

Xu,

Zhang,

et al. 2024

Biomedicines

View full text Add to dashboard Cite

The aim of this study is to investigate the role of the ADAMTS18 gene in regulating the renal development of mice. PAS staining was used to observe the kidney development of E12.5–E17.5 mice, while immunofluorescence staining and RT-PCR were used to observe the expression of ADAMTS18. Ureteric bud (UB) branches were observed using immunofluorescence staining using the UB marker E-cadherin, and the apoptosis and proliferation of posterior renal mesenchymal cells were analyzed using TUNEL and PH3 fluorescence staining. Flow cytometry was used to analyze the immune cell infiltration, and western blotting (WB) was used to analyze the expression of PD-1/PD-L1 and CTLA-4. As a result, the ADAMTS18 gene expression gradually increased as the kidney continued to mature during embryonic development. Compared with that in the control and vector groups, UB branching was significantly reduced in the ADAMTS18 deletion group (p < 0.05), but that deletion of ADAMTS18 did not affect posterior renal mesenchymal cell proliferation or apoptosis (p > 0.05). Compared with those in the control and vector groups, the proportion of embryonic kidney B cells and the proportion of CD8+ cells were significantly greater after ADAMTS18 was knocked down (p < 0.05), but the difference in neutrophil counts was not significant (p > 0.05). The WB analysis revealed that the PD-1/PD-L1 and CTLA-4 expression was significantly increased after ADAMTS18 was knocked down (p < 0.05). In conclusion, the ADAMTS18 gene may be involved in mice kidney development by regulating the immune microenvironment and activating immune checkpoints. Deletion of the ADAMTS18 gene may be unfavorable for kidney development.

show abstract

Section: Discussionsupporting

confidence: 75%

The Role of the ADAMTS18 Gene-Induced Immune Microenvironment in Mouse Kidney Development

Xu,

Zhang,

et al. 2024

Biomedicines

View full text Add to dashboard Cite

show abstract

“…In cell lines in vitro, it has been confirmed that ADAMTS18 methylation can occur in models of acute and chronic RF induced by lipopolysaccharide (LPS) and transforming growth factor (TGF)-β1, respectively. [11,12] The use of demethylating drugs, such as curcumin, can reverse acute and chronic RF by demethylating the ADAMTS18 gene.…”

Section: Introductionmentioning

confidence: 99%

The progression of obstructive renal fibrosis in rats is regulated by ADAMTS18 gene methylation in the embryonic kidney through the AKT/Notch pathway

Xu,

Zhang,

et al. 2023

J Biochem & Molecular Tox

Self Cite

View full text Add to dashboard Cite

This study aimed to explore the mechanism by which postembryonic renal ADAMTS18 methylation influences obstructive renal fibrosis in rats. After exposure to transforming growth factor (TGF)‐β1 during the embryonic period, analysis of postembryonic renal ADAMTS18 methylation and expression levels was conducted. Histological analysis was performed to assess embryonic kidney lesions and damage. Western blot analysis was used to determine the expression of renal fibrosis markers. Rats with ureteral obstruction and a healthy control group were selected. The methylation levels of ADAMTS18 in the different groups were analyzed. Western blot analysis and immunohistochemistry were performed to analyze the expression of renal fibrosis markers, and kidney‐related indicators were measured. Treatment with TGF‐β1 resulted in abnormal development of the postembryonic kidney, which was characterized by rough kidney surfaces with mild depressions and irregularities on the outer surface. TGF‐β1 treatment significantly promoted ADAMTS18 methylation and activated the protein kinase B (AKT)/Notch pathway. Ureteral obstruction was induced to establish a renal hydronephrosis model, which led to renal fibrotic injury in newborn rats. Overexpression of the ADAMTS18 gene alleviated renal fibrosis. The western blot results showed that compared to that in the control group, the expression of renal fibrosis markers was significantly decreased after ADAMTS18 overexpression, and there was a thicker renal parenchymal tissue layer and significantly reduced p‐AKT/AKT and Notch1 levels. TGF‐β1 can induce ADAMTS18 gene methylation in the postembryonic kidney, and the resulting downregulation of ADAMTS18 expression has long‐term effects on kidney development, potentially leading to increased susceptibility to obstructive renal fibrosis. This mechanism may involve activation of the AKT/Notch pathway. Reversing ADAMTS18 gene methylation may reverse this process.

show abstract

Curcumin Interferes with TGF- β 1-Induced Fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation

Cited by 2 publications

References 29 publications

The Role of the ADAMTS18 Gene-Induced Immune Microenvironment in Mouse Kidney Development

The Role of the ADAMTS18 Gene-Induced Immune Microenvironment in Mouse Kidney Development

The progression of obstructive renal fibrosis in rats is regulated by ADAMTS18 gene methylation in the embryonic kidney through the AKT/Notch pathway

Contact Info

Product

Resources

About