Up-regulation of the human-specific CHRFAM7A gene protects against renal fibrosis in mice with obstructive nephropathy

dc.contributor.authorZhou, Bingru
dc.contributor.authorZhang, Yudian
dc.contributor.authorDang, Xitong
dc.contributor.authorLi, Bowen
dc.contributor.authorWang, Hui
dc.contributor.authorGong, Shu
dc.contributor.authorLi, Siwen
dc.contributor.authorMeng, Fanyin
dc.contributor.authorXing, Juan
dc.contributor.authorLi, Tian
dc.contributor.authorHe, Longfei
dc.contributor.authorZou, Ping
dc.contributor.authorWan, Ying
dc.contributor.departmentMedicine, School of Medicine
dc.date.accessioned2023-10-23T12:39:51Z
dc.date.available2023-10-23T12:39:51Z
dc.date.issued2023
dc.description.abstractRenal fibrosis is a major factor in the progression of chronic kidney diseases. Obstructive nephropathy is a common cause of renal fibrosis, which is also accompanied by inflammation. To explore the effect of human-specific CHRFAM7A expression, an inflammation-related gene, on renal fibrosis during obstructive nephropathy, we studied CHRFAM7A transgenic mice and wild type mice that underwent unilateral ureteral obstruction (UUO) injury. Transgenic overexpression of CHRFAM7A gene inhibited UUO-induced renal fibrosis, which was demonstrated by decreased fibrotic gene expression and collagen deposition. Furthermore, kidneys from transgenic mice had reduced TGF-β1 and Smad2/3 expression following UUO compared with those from wild type mice with UUO. In addition, the overexpression of CHRFAM7A decreased release of inflammatory cytokines in the kidneys of UUO-injured mice. In vitro, the overexpression of CHRFAM7A inhibited TGF-β1-induced increase in expression of fibrosis-related genes in human renal tubular epithelial cells (HK-2 cells). Additionally, up-regulated expression of CHRFAM7A in HK-2 cells decreased TGF-β1-induced epithelial-mesenchymal transition (EMT) and inhibited activation f TGF-β1/Smad2/3 signalling pathways. Collectively, our findings demonstrate that overexpression of the human-specific CHRFAM7A gene can reduce UUO-induced renal fibrosis by inhibiting TGF-β1/Smad2/3 signalling pathway to reduce inflammatory reactions and EMT of renal tubular epithelial cells.
dc.eprint.versionFinal published version
dc.identifier.citationZhou B, Zhang Y, Dang X, et al. Up-regulation of the human-specific CHRFAM7A gene protects against renal fibrosis in mice with obstructive nephropathy. J Cell Mol Med. 2023;27(1):52-65. doi:10.1111/jcmm.17630
dc.identifier.urihttps://hdl.handle.net/1805/36551
dc.language.isoen_US
dc.publisherWiley
dc.relation.isversionof10.1111/jcmm.17630
dc.relation.journalJournal of Cellular and Molecular Medicine
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourcePMC
dc.subjectEpithelial-mesenchymal transition
dc.subjectInflammation
dc.subjectObstructive nephropathy
dc.subjectRenal fibrosis
dc.subjectUnilateral ureteral obstruction
dc.titleUp-regulation of the human-specific CHRFAM7A gene protects against renal fibrosis in mice with obstructive nephropathy
dc.typeArticle
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
JCMM-27-52.pdf
Size:
6.69 MB
Format:
Adobe Portable Document Format
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.99 KB
Format:
Item-specific license agreed upon to submission
Description: