Curcumin Interferes with TGF-β1-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

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Curcumin Interferes with TGF-β1-Induced Fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation

Original Article | Updated：2024-06-28

- Curcumin Interferes with TGF-β1-Induced Fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation
- Curcumin Interferes with TGF-β1-Induced Fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation
- 中国结合医学杂志（英文版） 2024年30卷第7期页码：600-607
- Affiliations：
  
  Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, National Urological Cancer Center, Beijing (100034), China
- Author bio：
  
  Dr. XU Ben, E-mail: xuben_pku@sina.com
- Funds：
  
  National Natural Science Foundation of China(82200740)
- DOI：10.1007/s11655-023-3564-9
  中图分类号：
- 纸质出版日期：2024-07，
  
  网络出版日期：2023-09-27，
  
  录用日期：2023-07-31
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Curcumin Interferes with TGF-β1-Induced Fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation[J]. 中国结合医学杂志（英文版）, 2024,30(7):600-607.

XU Ben, ZHANG Jia-en, YE Lin, et al. Curcumin Interferes with TGF-β1-Induced Fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation[J]. Chinese Journal of Integrative Medicine, 2024,30(7):600-607.
Curcumin Interferes with TGF-β1-Induced Fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation[J]. 中国结合医学杂志（英文版）, 2024,30(7):600-607. DOI： 10.1007/s11655-023-3564-9.

XU Ben, ZHANG Jia-en, YE Lin, et al. Curcumin Interferes with TGF-β1-Induced Fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation[J]. Chinese Journal of Integrative Medicine, 2024,30(7):600-607. DOI： 10.1007/s11655-023-3564-9.

摘要

Abstract

Objective:

To explore the molecular mechanism by which curcumin affects renal interstitial fibrosis (RIF) progression by regulating ADAM metallopeptidase with thrombospondin type 1 motif 18 (ADAMTS18) methylation.

Methods:

NRK-49F cells RIF model were induced with transforming growth factor β1 (TGF-β1). Effects of different concentrations of curcumin (0

and 30 μmol/L) on cell proliferation

cell cycle

cell apoptosis as well as cyclin D1 expression were analyzed by cell counting kit-8

flow cytometry and Western blot

respectively. ADAMTS18 methylation levels were determined by methylation-specific polymerase chain reaction. ADAMTS18

fibronectin (FN)

type Ⅰ collagen (Col-Ⅰ) and alpha-smooth muscle actin (α-SMA) mRNA and protein expressions were analyzed by real-time PCR (RT-PCR) and Western blot

respectively. Meanwhile

cells were treated with 50 mmol/L 5-aza-2'-deoxycytidine (5-aza-dC

demethylation agent) for 72 h. Effect of curcumin on extracellular matrix (ECM) deposition was evaluated by immunochemical staining and Western blot. NRK-49F cells were transfected with ADAMTS18 small interfering RNA and grouped into a normal control

ADAMTS18-knock-out (KO)

and ADAMTS18-KO+ 30 μmol/L curcumin groups

and whether curcumin can reverse the effect of ADAMTS18 knockdown on RIF was evaluated.

Results:

Compared with the control group

TGF-β1 significantly inhibited the proliferation of NRK-49F cells

blocked the G

phase

promoted cell apoptosis and inhibited cyclin D1 expression (

0.01). Among the different concentrations of curcumin

30 μmol/L curcumin significantly reversed these processes (

0.01). Immunochemical staining and Western blot results showed that curcumin significantly inhibited the deposition of FN

Col-Ⅰ and α-SMA (

0.01). Curcumin and 5-zaz-dC had synergistic effects

promoting ADAMTS18 expression

removing ADAMTS18 methylation

and reducing ECM deposition. ADAMTS18 knockdown promoted ECM accumulation

and curcumin reversed this process (

0.01).

Conclusion:

TGF-β1 induced fibrosis in NRK-49F cells. Curcumin promoted ADAMTS18 expression

reduced ECM accumulation

and alleviated RIF progression by inhibiting ADAMTS18 methylation.

关键词

Keywords

renal fibrosiscurcuminChinese medicineADAMTS18methylation modification

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