ArticleCell death and differentiation2024
TRIM65 deficiency alleviates renal fibrosis through NUDT21-mediated alternative polyadenylation.
Article in Cell death and differentiation, 2024. 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.
- TRIM65 accelerates VSMC-derived foam cell formation and arteriosclerosis progression by inhibiting mitophagy.Molecular and cellular biochemistry · 2026Article
- Article
- Alternative Polyadenylation Drives Runaway Pro-Inflammatory Macrophages in Periodontitis by Enabling Escape From miRNA Repression.Cell proliferation · 2026Article
- Regulated cell death: a multidimensional regulatory network in the pathogenesis of renal fibrosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Alternative polyadenylation releases PCBP1-mediated suppression of CFIm25 during macrophage differentiation.FEBS letters · 2026Article
- Involvement of c-Myc/WWP1/TRIM65 Axis in Renal Fibrosis.Biomolecules · 2026Article
- EphrinB2 Ameliorates Renal Fibrosis by Inhibiting the TGF-β/Smad3 Signaling Pathway and the Inflammation ResponseEndocrine, metabolic & immune disorders drug targets · 2026Article
- Luteolin and its derivatives: modulation of epithelial-mesenchymal transition in fibrosis and cancer.Frontiers in pharmacology · 2026Review
- The role of TRIM proteins in the pathogenesis of mycobacterium tuberculosis.Biology direct · 2025Review
- TRIM2 inhibits apoptosis by ubiquitinating BNIP3 to protect the intestine against ischemia-reperfusion injury in mice.Communications biology · 2025Article
- Renal tubular epithelial IGFBP7 interacts with PKM2 to drive renal lipid accumulation and fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- USP7 promotes endothelial activation to aggravate sepsis-induced acute lung injury through PDK1/AKT/NF-κB signaling pathway.Cell death discovery · 2025Article
- Protein lactylation in kidney diseases.Frontiers in cell and developmental biology · 2025Review
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Authors and funding
13 authors.
Funding
Abstract
Chronic kidney disease (CKD) is a major global health concern and the third leading cause of premature death. Renal fibrosis is the primary process driving the progression of CKD, but the mechanisms behind it are not fully understood, making treatment options limited. Here, we find that the E3 ligase TRIM65 is a positive regulator of renal fibrosis. Deletion of TRIM65 results in a reduction of pathological lesions and renal fibrosis in mouse models of kidney fibrosis induced by unilateral ureteral obstruction (UUO)- and folic acid. Through screening with a yeast-hybrid system, we identify a new interactor of TRIM65, the mammalian cleavage factor I subunit CFIm25 (NUDT21), which plays a crucial role in fibrosis through alternative polyadenylation (APA). TRIM65 interacts with NUDT21 to induce K48-linked polyubiquitination of lysine 56 and proteasomal degradation, leading to the inhibition of TGF-β1-mediated SMAD and ERK1/2 signaling pathways. The degradation of NUDT21 subsequently altered the length and sequence content of the 3'UTR (3'UTR-APA) of several pro-fibrotic genes including Col1a1, Fn-1, Tgfbr1, Wnt5a, and Fzd2. Furthermore, reducing NUDT21 expression via hydrodynamic renal pelvis injection of adeno-associated virus 9 (AAV9) exacerbated UUO-induced renal fibrosis in the normal mouse kidneys and blocked the protective effect of TRIM65 deletion. These findings suggest that TRIM65 promotes renal fibrosis by regulating NUDT21-mediated APA and highlight TRIM65 as a potential target for reducing renal fibrosis in CKD patients.
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