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TECs have regenerative capacity; however, maladaptive repair of TECs after injury leads to renal fibrosis, resulting in chronic kidney disease (CKD). We previously reported the specific expression of CD44 in failed\u2010repair TECs of rat CKD model induced by ischemia reperfusion injury. Here, we investigated the pathophysiological role of CD44 in renal fibrogenesis in allopurinol\u2010treated rat CKD model. Dilated or atrophic TECs expressing CD44 in fibrotic areas were collected by laser microdissection and subjected to microarray analysis. Gene ontology showed that extracellular matrix (ECM)\u2010related genes were upregulated and differentiation\u2010related genes were downregulated in dilated\/atrophic TECs. Ingenuity Pathway Analysis identified CD44 as an upstream regulator of fibrosis\u2010related genes, including <jats:italic>Fn1<\/jats:italic>, which encodes fibronectin. Immunohistochemistry demonstrated that dilated\/atrophic TECs expressing CD44 showed decreases in differentiation markers of TECs and clear expression of mesenchymal markers during basement membrane attachment. In situ hybridization revealed an increase in <jats:italic>Fn1<\/jats:italic> mRNA in the cytoplasm of dilated\/atrophic TECs, whereas fibronectin was localized in the stroma around these TECs, supporting the production\/secretion of ECM by dilated\/atrophic TECs. Overall, these data indicated that dilated\/atrophic TECs underwent a partial epithelial\u2013mesenchymal transition (pEMT) and that CD44 promoted renal fibrogenesis via induction of ECM production in failed\u2010repair TECs exhibiting pEMT. CD44 was detected in the urine and serum of APL\u2010treated rats, which may reflect the expression of CD44 in the kidney.<\/jats:p>","DOI":"10.1002\/jat.4554","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T01:57:20Z","timestamp":1698199040000},"page":"455-469","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Role of CD44 expressed in renal tubules during maladaptive repair in renal fibrogenesis in an allopurinol\u2010induced rat model of chronic kidney disease"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4184-0367","authenticated-orcid":false,"given":"Kohei","family":"Matsushita","sequence":"first","affiliation":[{"name":"Division of Pathology National Institute of Health Sciences  Kawasaki Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1646-4603","authenticated-orcid":false,"given":"Takeshi","family":"Toyoda","sequence":"additional","affiliation":[{"name":"Division of Pathology National Institute of Health Sciences  Kawasaki Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotoshi","family":"Akane","sequence":"additional","affiliation":[{"name":"Division of Pathology National Institute of Health Sciences  Kawasaki Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Morikawa","sequence":"additional","affiliation":[{"name":"Division of Pathology National Institute of Health Sciences  Kawasaki Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4454-3838","authenticated-orcid":false,"given":"Kumiko","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Division of Pathology National Institute of Health Sciences  Kawasaki Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-017-0536-3"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1996.298"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.asn.0000067652.51441.21"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.208"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-018-0605-5"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099802"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep40183"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4309"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-019-02598-0"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/ajkd.2002.30563"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-06-0011"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117589"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2017.01.005"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000589"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017030334"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-022-02701-y"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/01913123.2018.1501125"},{"key":"e_1_2_8_19_1","unstructured":"Japan Toxicogenomics Project. 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