ArticleThe Journal of pathology2012
Loss of glutathione S-transferase A4 accelerates obstruction-induced tubule damage and renal fibrosis.
Article in The Journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Ferroptosis in kidney disease.Nature reviews. Nephrology · 2026Review
- The Link Between Serum Copper and Diabetic Kidney Disease: A Plasma Proteomic Perspective.Journal of diabetes research · 2026Article
- Direct androgen receptor control of sexually dimorphic gene expression in the mammalian kidney.Developmental cell · 2023Article
- Inhibition of ACSL4 ameliorates tubular ferroptotic cell death and protects against fibrotic kidney disease.Communications biology · 2023Article
- Direct androgen receptor regulation of sexually dimorphic gene expression in the mammalian kidney.bioRxiv : the preprint server for biology · 2023Article
- Protective Effects of Carnosol on Renal Interstitial Fibrosis in a Murine Model of Unilateral Ureteral Obstruction.Antioxidants (Basel, Switzerland) · 2022Article
- Sex differences in resilience to ferroptosis underlie sexual dimorphism in kidney injury and repair.Cell reports · 2022Article
- In VivoInternational journal of molecular sciences · 2019Article
- Metabolic consequences of cystinuria.BMC nephrology · 2019Article
- Reduced Expression of Glutathione S-TransferaseJournal of the American Society of Nephrology : JASN · 2018Article
- Hydrodynamic Renal Pelvis Injection for Non-viral Expression of Proteins in the Kidney.Journal of visualized experiments : JoVE · 2018Article
- Preclinical and clinical advances in transposon-based gene therapy.Bioscience reports · 2017Review
- Yap/Taz Deletion in GliJournal of the American Society of Nephrology : JASN · 2017Article
- Kidney-specific transposon-mediated gene transfer in vivo.Scientific reports · 2017Article
- Effect of ALDH2 on High Glucose-Induced Cardiac Fibroblast Oxidative Stress, Apoptosis, and Fibrosis.Oxidative medicine and cellular longevity · 2017Article
- CD11c⁺ CD8⁺ T Cells Reduce Renal Fibrosis Following Ureteric Obstruction by Inducing Fibroblast Apoptosis.International journal of molecular sciences · 2016Article
- Comparative Microarray Analysis Identifies Commonalities in Neuronal Injury: Evidence for Oxidative Stress, Dysfunction of Calcium Signalling, and Inhibition of Autophagy-Lysosomal Pathway.Neurochemical research · 2016Review
- piggyBac-ing models and new therapeutic strategies.Trends in biotechnology · 2015Review
- Protective role of insulin-like growth factor-1 receptor in endothelial cells against unilateral ureteral obstruction-induced renal fibrosis.The American journal of pathology · 2015Article
- Autophagy is a regulator of TGF-β1-induced fibrogenesis in primary human atrial myofibroblasts.Cell death & disease · 2015Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Glutathione transferase isozyme A4 (GSTA4) exhibits high catalytic efficiency to metabolize 4-hydroxynonenal (4-HNE), a highly reactive lipid peroxidation product that has been implicated in the pathogenesis of various chronic diseases. We investigated the role of 4-HNE in the mechanisms of unilateral ureteral obstruction (UUO)-induced fibrosis and its modulation by GSTA4-4 in a mouse model. Our data indicate that after UUO, accumulation of 4-HNE and its adducts were increased in renal tissues, with a concomitant decrease in the expression of GSTA4-4 in mice. As compared to wild-type (WT) mice, UUO caused an increased expression of fibroblast markers in the interstitium of GSTA4 KO mice. Additionally, increased autophagy and tubular cell damage were more severe in UUO-treated GSTA4 KO mice than in WT mice. Furthermore, GSK-3β phosphorylation and expression of Snail, a regulator of E-cadherin and Occludin, was found to be significantly higher in UUO-inflicted GSTA4 KO mice. GSTA4 over-expression prevented 4-HNE-induced autophagy activation, tubular cell damage and Snail nuclear translocation in vitro. The effects of long-term expression of GSTA4 in restoration of UUO-induced damage in mice with the GSTA4 inducible transposon system indicated that release of obstruction after 3 days of UUO resulted in the attenuation of interstitial SMAα and collagen I expression. This transposon-delivered GSTA4 expression also suppressed UUO-induced loss of tubular cell junction markers and autophagy activation. Together, these results indicate that 4-HNE significantly contributes to the mechanisms of tubule injury and fibrosis and that these effects can be inhibited by the enhanced expression of GSTA4-4.
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