{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T17:05:36Z","timestamp":1773335136258,"version":"3.50.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81860136, 8246030042"],"award-info":[{"award-number":["81860136, 8246030042"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","award":["2022BEG03121, 2025AAC050050, 2025AAC030405, 2024AAC03511"],"award-info":[{"award-number":["2022BEG03121, 2025AAC050050, 2025AAC030405, 2024AAC03511"]}],"id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the potential crosstalk between TrkA, the high-affinity nerve growth factor receptor (NGFR), and cyclin-dependent kinase 5 (CDK5) in the pathogenesis of diabetic kidney disease (DKD). Furthermore, this study aims to evaluate the therapeutic potential of targeting TrkA in DKD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The renal transcriptional profiles were evaluated in db\/db mice and controls. High glucose (HG) stimulation was used to induce an\n                      <jats:italic>in vitro<\/jats:italic>\n                      model of podocyte injury. The therapeutic effects of the TrkA inhibitor GW441756 were evaluated in both DKD model mice and HG-stimulated podocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>RNA sequencing detected NGFR upregulation in db\/db mice. Phosphorylation of TrkA (Tyr490) increased in HG-stimulated podocytes, and TrkA overexpression aggravated HG-induced injury. Mechanistically, TrkA activation functionally links to CDK5 in the pathogenesis of DKD. Specifically, phosphorylation of TrkA at Tyr490 triggers the activation of the downstream ERK\/EGR1 pathway. The accumulation of p35 activated CDK5, resulting in an inflammation-mediated podocyte injury. The TrkA inhibitor reduced its phosphorylation and attenuated downstream inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest a TrkA-p35\/CDK5 axis contributes to podocyte inflammation and injury, connecting neurotrophic signalling and renal metabolic inflammation through a novel mechanism. This work indicates that TrkA represents a potential therapeutic target for DKD therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1791283","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T05:27:39Z","timestamp":1773293259000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Unveiling the TrkA-p35\/CDK5 axis: a novel therapeutic target in diabetic kidney disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Wenbo","family":"Xia","sequence":"first","affiliation":[{"name":"People\u2019s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University","place":["Yinchuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Wang","sequence":"additional","affiliation":[{"name":"People\u2019s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University","place":["Yinchuan, 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