ArticleThe Journal of clinical investigation2024
The secreted micropeptide C4orf48 enhances renal fibrosis via an RNA-binding mechanism.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Renal IGFBP6 Interacts With THBS1 to Drive Renal Cellular Senescence and Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Single Cell Transcriptomics and Surface Protein Expression Reveal Distinct Cellular and Molecular Phenotypes in Human RPESC-RPE and PSC-RPE.bioRxiv : the preprint server for biology · 2026Article
- Single-Cell Dissection of the Biological Function and Molecular Features Underlying the Micropeptide LSMEM1 in Kidney.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ewing sarcoma depends on C4orf48/NICOL, a NELL2 cofactor regulated by Hippo signaling.Cellular signalling · 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
- Mitochondria-related gene-based molecular subtypes of lung adenocarcinoma and their prognostic implications.Scientific reports · 2025Article
- Single-cell RNA sequencing identifies CXADR as a fate determinant of the placental exchange surface.Nature communications · 2025Article
- Yishen-Huoxue formula alleviates renal interstitial fibrosis by attenuating hypoxia-induced renal cell injury and promoting angiogenesis via miR-210/HIF-1α pathway.Frontiers in medicine · 2025Article
- Article
- Mendelian Randomization and Transcriptome Data Analysis Reveal Bidirectional Causal Relationships and Mechanisms between Type 2 Diabetes and Gastric Cancer.Current medicinal chemistry · 2025Article
- Micropeptides Encoded by Noncoding RNAs: Biological Functions and Roles in Diseases.Research (Washington, D.C.) · 2025Review
Corrections and comments
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Authors and funding
22 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal interstitial fibrosis is an important mechanism in the progression of chronic kidney disease (CKD) to end-stage kidney disease. However, we lack specific treatments to slow or halt renal fibrosis. Ribosome profiling identified upregulation of a secreted micropeptide, C4orf48 (Cf48), in mouse diabetic nephropathy. Cf48 RNA and protein levels were upregulated in tubular epithelial cells in human and experimental CKD. Serum Cf48 levels were increased in human CKD and correlated with loss of kidney function, increasing CKD stage, and the degree of active interstitial fibrosis. Cf48 overexpression in mice accelerated renal fibrosis, while Cf48 gene deletion or knockdown by antisense oligonucleotides significantly reduced renal fibrosis in CKD models. In vitro, recombinant Cf48 (rCf48) enhanced TGF-β1-induced fibrotic responses in renal fibroblasts and epithelial cells independently of Smad3 phosphorylation. Cellular uptake of Cf48 and its profibrotic response in fibroblasts operated via the transferrin receptor. RNA immunoprecipitation-sequencing identified Cf48 binding to mRNA of genes involved in the fibrotic response, including Serpine1, Acta2, Ccn2, and Col4a1. rCf48 binds to the 3'UTR of Serpine1 and increases mRNA half-life. We identify the secreted Cf48 micropeptide as a potential enhancer of renal fibrosis that operates as an RNA-binding peptide to promote the production of extracellular matrix.
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