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(Landmark Ed)"],"abstract":"<jats:p>Background: Kidney stones are a globally prevalent condition, but their pathogenesis remains incompletely understood. This study aimed to identify and validate key genes implicated in kidney stone formation through sequencing data analysis, offering novel molecular targets for elucidating the underlying pathogenic mechanisms. Methods: A mouse model of kidney stones was established, and perinephrolithic renal tissue samples were obtained from patients who underwent nephrectomy due to renal dysfunction caused by kidney stones. Transcriptome sequencing was employed to identify differentially expressed genes (DEGs) common to both human and mouse samples. Expression of DEGs in kidney stone specimens was validated using real-time quantitative polymerase chain reaction (qRT-PCR), western blotting, and immunofluorescence (IF). Concurrently, Gene Ontology (GO) and Kyoto Kncyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to investigate functional and pathway associations of the DEGs. Results: Transcriptome sequencing identified eight genes consistently upregulated in both humans and mice: COL3A1, TYROBP, MMP2, BASP1, COL5A1, ITGAX, C1QC, and S100A8. qRT-PCR results demonstrated elevated mRNA levels of C1QC and COL3A1 in the perinephrolithic renal tissues of the mouse model. Western blotting confirmed upregulation of COL3A1 at the protein level, and IF staining further verified the specific enrichment of COL3A1 in the renal tissues of the mouse kidney stone model. GO and KEGG enrichment analyses revealed significant associations between the DEGs and immune-related signaling pathways, as well as biological processes involved in extracellular matrix (ECM) remodeling. Conclusions: These findings suggest that the ongoing upregulation of COL3A1 could be a key factor in the pathogenesis of kidney stone. Functional enrichment analyses indicate that COL3A1 may promote stone deposition and progression by regulating ECM remodeling and the immune response . These results provide new insights into the molecular mechanisms underlying kidney stone formation.<\/jats:p>","DOI":"10.31083\/fbl51232","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T07:25:36Z","timestamp":1780125936000},"source":"Crossref","is-referenced-by-count":0,"title":["Upregulation of COL3A1 is a Key Driver in Kidney Stone Formation"],"prefix":"10.31083","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4945-2078","authenticated-orcid":true,"given":"Hua","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Urology, Affiliated Zhongda Hospital of Southeast University, 210009 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanji","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Medicine, Southeast University, 210009 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ji","sequence":"additional","affiliation":[{"name":"School of Medicine, Southeast University, 210009 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anyang","family":"Chou","sequence":"additional","affiliation":[{"name":"School of Medicine, Southeast University, 210009 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3878-5224","authenticated-orcid":true,"given":"Weipu","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Urology, Affiliated Zhongda Hospital of Southeast University, 210009 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3572-6886","authenticated-orcid":true,"given":"Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, Affiliated Zhongda Hospital of Southeast University, 210009 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Urology, Nanjing Hospital of Chinese Medicine, 210000 Nanjing, Jiangsu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Jahrreiss V, Seitz C, Quhal F. 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