TGF-β1 induces ROS to activate ferroptosis via the ERK1/2-WISP1 pathway to promote the progression of renal tubular epithelial cell fibrosis
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View abstract on PubMed
Summary
This summary is machine-generated.Transforming growth factor-beta 1 (TGF-β1) triggers kidney fibrosis by inducing ferroptosis, a cell death process, through the ERK1/2-WISP1 pathway. This study reveals a novel mechanism in chronic kidney disease progression.
Area Of Science
- Nephrology
- Cell Biology
- Biochemistry
Background
- Chronic kidney disease (CKD) progression is often marked by renal fibrosis.
- Renal fibrosis involves excessive extracellular matrix deposition and is linked to ferroptosis.
- The role of transforming growth factor-beta 1 (TGF-β1) in inducing ferroptosis and fibrosis in renal tubular epithelial cells requires further elucidation.
Purpose Of The Study
- To investigate the mechanism by which TGF-β1 induces ferroptosis and contributes to renal tubular epithelial cell fibrosis.
- To identify key signaling pathways involved in TGF-β1-induced renal fibrosis and ferroptosis.
Main Methods
- Bioinformatics analysis to identify fibrosis-related genes.
- Establishment of an in vitro TGF-β1-induced fibrosis model using HK-2 cells.
- Intervention with Fer-1, N-acetylcysteine (NAC), and PD98059; WISP1 knockdown via shRNA lentivirus.
- Assessment of cell morphology, ferroptosis markers (Fe2+, MDA, GSH, LPO), reactive oxygen species (ROS) levels, and Western blotting for ERK1/2, WISP1, GPX4, and PRDX4.
Main Results
- TGF-β1 induced HK-2 cell transformation into fibroblast-like cells, increasing ROS levels, activating the ERK1/2-WISP1 pathway, and upregulating ferroptosis and fibrosis markers.
- Inhibitors (Fer-1, NAC, PD98059) and WISP1 knockdown effectively suppressed TGF-β1-induced cell changes, ferroptosis, and fibrosis.
- WISP1 knockdown significantly reduced cell transformation, ferroptosis, and expression of related factors.
Conclusions
- TGF-β1 induces renal tubular epithelial cell fibrosis by promoting ROS production and ferroptosis via the ERK1/2-WISP1 signaling pathway.
- Targeting the ERK1/2-WISP1 pathway and ferroptosis presents a potential therapeutic strategy for renal fibrosis in CKD.
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