C/EBPβ mediates expressions of downstream inflammatory factors of the tumor necrosis factor-α signaling pathway in renal tubular epithelial cells with NPHP1 knockdown
10.12122/j.issn.1673-4254.2024.01.18
- VernacularTitle:C/EBPβ介导NPHP1敲低的肾小管上皮细胞TNF-α通路下游炎症因子的表达
- Author:
Danmei HUANG
1
;
Yaqing LIU
;
Dantong LI
;
Jinglan ZHANG
;
Yichen YANG
;
Liangzhong SUN
Author Information
1. 南方医科大学南方医院儿科,广东 广州 510515
- Keywords:
nephronophthisis;
tumor necrosis factor-α;
C/EBPβ;
inflammatory factor;
NPHP1
- From:
Journal of Southern Medical University
2024;44(1):156-165
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the activation of tumor necrosis factor-α(TNF-α)signaling pathway and the expressions of the associated inflammatory factors in NPHP1-defective renal tubular epithelial cells.Methods A human proximal renal tubular cell(HK2)model of lentivirus-mediated NPHP1 knockdown(NPHP1KD)was constructed,and the expressions of TNF-α,p38,and C/EBPβ and the inflammatory factors CXCL5,CCL20,IL-1β,IL-6 and MCP-1 were detected using RT-qPCR,Western blotting or enzyme-linked immunosorbent assay.A small interfering RNA(siRNA)was transfected in wild-type and NPHP1KDHK2 cells,and the changes in the expressions of TNF-α,p38,and C/EBPβ and the inflammatory factors were examined.Results NPHP1KDHK2 cells showed significantly increased mRNA expressions of TNF-α,C/EBPβ,CXCL5,IL-1β,and IL-6(P<0.05),protein expressions of phospho-p38 and C/EBPβ(P<0.05),and IL-6 level in the culture supernatant(P<0.05),and these changes were significantly blocked by transfection of cells with siRNA-C/EBPβ(P<0.05).Conclusion TNF-α signaling pathway is activated and its associated inflammatory factors are upregulated in NPHP1KDHK2 cells,and C/EBPβ may serve as a key transcription factor to mediate these changes.
