Please use this identifier to cite or link to this item: https://repository.monashhealth.org/monashhealthjspui/handle/1/51673
Title: The secreted micropeptide C4orf48 enhances renal fibrosis via an RNA-binding mechanism.
Authors: Yang J. ;Zhuang H.;Li J.;Nunez-Nescolarde A.B.;Luo N.;Chen H.;Li A.;Qu X.;Wang Q.;Fan J.;Bai X.;Ye Z.;Gu B.;Meng Y.;Zhang X.;Wu D.;Sia Y.;Jiang X.;Chen W.;Combes A.N.;Nikolic-Paterson D.J. ;Yu X.
Monash Health Department(s): Nephrology
Institution: (Yang, Luo, Fan, Chen) Department of Nephrology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
(Zhuang, Jiang) Department of Pediatrics, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
(Li, Wang, Bai, Ye, Yu) Department of Nephrology, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
(Nunez-Nescolarde) Department of Anatomy and Developmental Biology, Monash Biomedicine Discove, Monash University, Clayton, Australia
(Chen) Second Clinical College, Guangdong Medical University, Dongguan, China
(Li, Nikolic-Paterson) Department of Nephrology, Monash Health and Monash University Department of Medicine, Clayton, Australia
(Qu, Combes) Department of Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Australia
(Gu, Meng) Department of Clinical Laboratory, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
(Zhang, Wu) Department of Biostatistics, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, United States
(Sia) School of Life Science, Tsinghua University, Beijing, China
Issue Date: 23-Apr-2024
Copyright year: 2024
Place of publication: United States
Publication information: The Journal of Clinical Investigation. 134(10) (no pagination), 2024. Date of Publication: 16 Apr 2024.
Journal: The Journal of Clinical Investigation
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-beta1-induced fibrotic responses in renal fibroblasts and epithelial cells independent of Smad3 phosphorylation. Cellular uptake of Cf48 and its pro-fibrotic 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'-untranslated region of Serpine1 and increases mRNA half-life. We identify the secreted Cf48 micropeptide as a potential enhancer of renal fibrosis which operates as an RNA-binding peptide to promote the production of extracellular matrix.
DOI: http://monash.idm.oclc.org/login?url=https://dx.doi.org/10.1172/JCI178392
PubMed URL: 38625739 [https://www.ncbi.nlm.nih.gov/pubmed/?term=38625739]
URI: https://repository.monashhealth.org/monashhealthjspui/handle/1/51673
Type: Article
Subjects: chronic kidney failure
diabetic nephropathy
end stage renal disease
kidney fibrosis
kidney function
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