ArticleThe Journal of clinical investigation2025
ZDHHC18 promotes renal fibrosis development by regulating HRAS palmitoylation.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- The role of protein palmitoylation in disease pathogenesis and therapeutic innovation.Annals of medicine · 2026Review
- zDHHC21 loss of function activates lung fibroblasts by regulating PTEN palmitoylation.American journal of respiratory cell and molecular biology · 2026Article
- Article
- Targeting posttranslational modifications of oxidative stress pathways for the treatment of diabetic nephropathy.Journal of pharmaceutical analysis · 2026Review
- Exploring the functional role of palmitoylation genes in clear cell renal cell carcinoma and their impact on tumor microenvironment.BMC genomic data · 2026Article
- Multimodal AI-Driven Identification of Dehydrocostus Lactone as a Potent Renal Fibrosis Attenuator Targeting IQGAP1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Palmitoylation in Renal Physiology and Pathology.Biomolecules · 2026Review
- Regulatory networks of post-translational modifications in diabetic kidney disease: from pathogenic mechanisms to therapeutic frontiers.Frontiers in endocrinology · 2026Review
- Post-translational protein S-palmitoylation in renal tubular injury: mechanisms and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- RP-182 alleviated obstruction-induced renal fibrosis by reprogramming CD206Frontiers in pharmacology · 2026Article
- Potential therapeutic target in oncology: Protein palmitoylation (Review).Oncology reports · 2025Review
- Palmitoylation: an emerging therapeutic target bridging physiology and disease.Cellular & molecular biology letters · 2025Review
- ZDHHC14-Mediated TEAD4 Palmitoylation Drives Th17 Cell Recruitment in Renal Immunopathology.Research (Washington, D.C.) · 2025Article
- Enzymatic post-translational modifications of proteins in chronic kidney disease: mechanisms, regulation, and clinical significance.Frontiers in pharmacology · 2025Review
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Authors and funding
11 authors.
Funding
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Abstract
Fibrosis is the final common pathway leading to end-stage chronic kidney disease (CKD). However, the function of protein palmitoylation in renal fibrosis and the underlying mechanisms remain unclear. In this study, we observed that expression of the palmitoyltransferase ZDHHC18 was significantly elevated in unilateral ureteral obstruction (UUO) and folic acid-induced (FA-induced) renal fibrosis mouse models and was significantly upregulated in fibrotic kidneys of patients with CKD. Functionally, tubule-specific deletion of ZDHHC18 attenuated tubular epithelial cells' partial epithelial-mesenchymal transition (EMT) and then reduced the production of profibrotic cytokines and alleviated tubulointerstitial fibrosis. In contrast, ZDHHC18 overexpression exacerbated progressive renal fibrosis. Mechanistically, ZDHHC18 catalyzed the palmitoylation of HRAS, which was pivotal for its translocation to the plasma membrane and subsequent activation. HRAS palmitoylation promoted downstream phosphorylation of MEK/ERK and further activated Ras-responsive element-binding protein 1 (RREB1), enhancing SMAD binding to the Snai1 cis-regulatory regions. Taken together, our findings suggest that ZDHHC18 plays a crucial role in renal fibrogenesis and represents a potential therapeutic target for combating kidney fibrosis.
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