{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:03:09Z","timestamp":1789041789416,"version":"build-2803163510"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Otago Medical Research Foundation and the Maurice and Phyllis Paykel Trust"},{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008247","name":"University of Otago","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008247","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder caused by mutations in PKD1 or PKD2. The PAX2 and PAX8 genes encode transcription factors required for kidney development, but their role in ADPKD remains unclear. We hypothesized that PAX2 and PAX8 contribute to ADPKD cystogenesis through distinct and overlapping mechanisms. Using immunofluorescence, PAX2 and PAX8 expression was assessed in human ADPKD kidney tissues. Nuclear PAX2 expression, and cytoplasmic PAX8 expression were found to be up-regulated in cyst-lining epithelial cells. Furthermore, using siRNA-mediated knockdown of PAX2 and PAX8, significantly reduced 3D spheroid growth was observed in MDCK, WT9\u20137, and WT9\u201312 renal epithelial cell line models. RNA sequencing after individual and combined knockdown of PAX2 and PAX8 in WT9\u20137 and WT9\u201312 cells identified differentially expressed genes and enriched pathways, revealing that PAX2 regulates pathways related to embryonic development, endoplasmic reticulum stress, and cilia. In contrast, PAX8 regulates cell cycle and adhesion pathways, while dual knockdown of PAX2 and PAX8 impacted extracellular matrix organization pathways. Several genes, including AGO2 and WWTR1, which were previously found to exhibit expression changes in human ADPKD tissues were co-regulated by both factors, suggesting their upregulation in ADPKD may be due to PAX co-expression. Overall, we found PAX2 and PAX8 regulated both unique and overlapping gene networks known to promote ADPKD cystic epithelial growth. Their differential expression patterns and combined impact on extracellular matrix remodelling highlight their potential as therapeutic targets. These findings advance our understanding of ADPKD pathogenesis, and suggest potential avenues for targeted intervention.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf205","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T12:38:08Z","timestamp":1767098288000},"source":"Crossref","is-referenced-by-count":2,"title":["<i>PAX<\/i>\n                    gene expression in autosomal dominant polycystic kidney disease contributes to cyst expansion and regulates a gene network associated with cyst growth"],"prefix":"10.1093","volume":"35","author":[{"given":"Qi","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Dunedin School of Medicine, 56 Hanover Street, University of Otago , Dunedin ,","place":["9016, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cherie","family":"Stayner","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Dunedin School of Medicine, 56 Hanover Street, University of Otago , Dunedin ,","place":["9016, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Dunedin School of Medicine, 56 Hanover Street, University of Otago , Dunedin ,","place":["9016, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Gimenez","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Dunedin School of Medicine, 56 Hanover Street, University of Otago , Dunedin ,","place":["9016, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6824-8761","authenticated-orcid":false,"given":"Michael R","family":"Eccles","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, Dunedin School of Medicine, 56 Hanover 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