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However, the exact underlying mechanism remains elusive. This study employs transcriptome sequencing and identifies\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010Klotho (KLB) as the critical target responsible for the role of Smg in kidney protection. Smg treatment alleviates diabetic kidney injury by inhibiting ferroptosis in patients, animal models, and HK\u20102 cells. Notably, Smg treatment significantly increases the mRNA expression of KLB through the activation of the cyclic adenosine monophosphate (cAMP) signaling pathway, specifically through the phosphorylation of protein kinase A (PKA) and cAMP\u2010response element\u2010binding protein (CREB). Subsequently, the adenosine monophosphate\u2010activated protein kinase (AMPK) signaling pathway is activated, reprograming the key metabolic processes of ferroptosis such as iron metabolism, fatty acid synthesis, and the antioxidant response against lipid peroxidation. Suppression of ferroptosis by Smg further attenuates renal inflammation and fibrosis. This work highlights the potential of GLP\u20101RAs and KLB targeting as promising therapeutic approaches for DKD management.\n                  <\/jats:p>","DOI":"10.1002\/advs.202409781","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T10:09:08Z","timestamp":1733306948000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":57,"title":["GLP\u20101 Receptor Agonists Alleviate Diabetic Kidney Injury via\n                    <i>\u03b2<\/i>\n                    \u2010Klotho\u2010Mediated Ferroptosis Inhibition"],"prefix":"10.1002","volume":"12","author":[{"given":"Shasha","family":"Tian","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Hormones and Development, Chu Hsien\u2010I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Key Laboratory of Metabolic Diseases Tianjin Medical University Tianjin 300134 China"},{"name":"Department of Nephrology The Fifth Hospital of Shanxi Medical University (Shanxi Provincial People's Hospital)  Taiyuan Shanxi 030000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saijun","family":"Zhou","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Hormones and Development, Chu Hsien\u2010I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Key Laboratory of Metabolic Diseases Tianjin Medical University Tianjin 300134 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixi","family":"Wu","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Hormones and Development, Chu Hsien\u2010I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Key Laboratory of Metabolic Diseases Tianjin Medical University Tianjin 300134 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"lin","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Hormones and Development, Chu Hsien\u2010I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Key Laboratory of Metabolic Diseases Tianjin Medical University Tianjin 300134 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongdan","family":"Wang","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Hormones and Development, Chu Hsien\u2010I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Key Laboratory of Metabolic Diseases Tianjin Medical University Tianjin 300134 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haizhen","family":"Sun","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Hormones and Development, Chu Hsien\u2010I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Key Laboratory of Metabolic Diseases Tianjin Medical University Tianjin 300134 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A\u2010Shan\u2010Jiang","family":"A\u2010Ni\u2010Wan","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Hormones and Development, Chu Hsien\u2010I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Key Laboratory of Metabolic Diseases Tianjin Medical University Tianjin 300134 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaru","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science &amp; 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