{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T15:35:28Z","timestamp":1789486528961,"version":"build-2803163510"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Proximal tubular epithelial cells (PTECs) are more susceptible to damage due to their high energy requirements. The apoptosis of PTECs has been thought as the main cause of diabetic kidney disease (DKD). However, the reported apoptotic rate was around 5%-25%, suggesting that apoptosis alone cannot fully explain disease progression. An important question is arised: what happens to these surviving PTECs? Studies showed that many surviving PTECs lost their mature phenotype and entered a dedifferentiated, scattered tubular cell-like state. This adaptive change may offer some protective benefit. However, chronic persistent high-glucose stimulates those dedifferentiated PTECs (dPTECs) to secrete proinflammatory or profibrotic factors and drove tubulointerstitial fibrosis, even renal failure. Therefore, PTECs are not only the \u201cvictim\u201d, but also the \u201cdriver\u201d in the development of DKD. Current therapeutic strategies, including SGLT2 inhibitors, gut microbiota modulation, and traditional Chinese medicine, may improve the pathological microenvironment associated with dPTECs, but direct evidence that they can reverse PTEC dedifferentiation remains limited. This review summarizes the characteristics and regulatory mechanisms of dPTECs in DKD, discusses their pathogenic roles, heterogeneity, repair potential, and therapeutic relevance, aiming to provide new perspectives for redirecting maladaptive tubular remodeling toward renal repair.<\/jats:p>","DOI":"10.3389\/fendo.2026.1965334","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:07:37Z","timestamp":1789477657000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dedifferentiated proximal tubular epithelial cells in diabetic kidney disease: pathogenic roles, repair potential, and therapeutic implications"],"prefix":"10.3389","volume":"17","author":[{"given":"Lei","family":"Chen","sequence":"first","affiliation":[{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabology, Shandong Key Laboratory of Rheumatic Diseaseand Translational Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Nephrology","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabology, Shandong Key Laboratory of Rheumatic Diseaseand Translational Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Institute of Nephrology","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of 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