{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:24:11Z","timestamp":1790774651116,"version":"4.1.0"},"reference-count":45,"publisher":"Georg Thieme Verlag KG","issue":"03","funder":[{"name":"Three New Projects of Yijishan Hospital, The First Affiliated\n                        Hospital of Wannan Medical Colleg","award":["Y2205"],"award-info":[{"award-number":["Y2205"]}]},{"name":"Suzhou Science and Technology Plan Project","award":["SKJY2021082"],"award-info":[{"award-number":["SKJY2021082"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diabetic foot ulcer (DFU) represents a severe\n                        complication of diabetes, mainly caused by peripheral vascular occlusion and\n                        infection, presenting significant clinical challenges in treatment and\n                        potentially resulting in gangrene, amputation, or even fatality. This study\n                        aimed to investigate the involvement and underlying mechanisms of\n                        Meteorin-like (Metrnl) in the pathogenic process of DFU.<\/jats:p><jats:p> Mice underwent diabetes induction by streptozotocin,\n                        while human umbilical vein endothelial cells (HUVECs) were exposed to 5.5,\n                        10, 20 or 40 mM glucose. HUVECs were transfected with negative or Metrnl or\n                        si-nc or si-Metrnl plasmids via Lipofectamine 2000.<\/jats:p><jats:p> The expression of Metrnl was down-regulated in both\n                        patients and the murine model of DFU. Elevated glucose levels diminished\n                        Metrnl through enhanced Metrnl ubiquitination. The suppression of Metrnl\n                        exacerbated foot ulcer in the mouse model of DFU. Metrnl alleviated\n                        oxidative stress and ferroptosis in the DFU model by inhibiting\n                        mitochondrial damage. Metrnl induced liver kinase B1 (LKB1)\/AMP-activated\n                        protein kinase (AMPK) signaling in the DFU model. LKB1 attenuated the\n                        effects of Metrnl on oxidative stress and ferroptosis in the DFU model.<\/jats:p><jats:p>\u2002 The data cumulatively demonstrate that Metrnl\n                        ameliorates ferroptosis in the DFU model by inhibiting mitochondrial damage\n                        via LKB1\/AMPK signaling, suggesting that targeting Metrnl may emerge as a\n                        potential preventive approach against ferroptosis of DFU or other\n                        diabetes.<\/jats:p>","DOI":"10.1055\/a-2502-8712","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T23:51:49Z","timestamp":1741823509000},"page":"120-132","source":"Crossref","is-referenced-by-count":10,"title":["Metrnl Ameliorates Ferroptosis in Model of Diabetic Foot Ulcer\n                    Through the Inhibition of Mitochondrial Damage via LKB1\/AMPK\n                    Signaling"],"prefix":"10.1055","volume":"133","author":[{"given":"Xiangjian","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Second Affiliated Hospital of Soochow\n                    University, Suzhou, China"},{"name":"Department of Endocrinology, Yijishan Hospital of Wannan Medical\n                    College, Wuhu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichen","family":"PU","sequence":"additional","affiliation":[{"name":"Drug Evaluation Center, Yijishan Hospital of Wannan Medical College,\n                    Wuhu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Yijishan Hospital of Wannan Medical\n                    College, Wuhu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Yijishan Hospital of Wannan Medical\n                    College, Wuhu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7800-1001","authenticated-orcid":false,"given":"Ying","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Second Affiliated Hospital of Soochow\n                    University, Suzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"e14801","DOI":"10.1111\/iwj.14801","article-title":"Multi-disciplinary diabetic limb salvage programme in octogenarians with\n                    diabetic foot ulcers is not futile: An observational study with historical\n                    controls","volume":"21","author":"L Ge","year":"2024","journal-title":"Int Wound J"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"46","DOI":"10.3923\/pjbs.2024.46.51","article-title":"Implication of low plasma arginine among patients with diabetic foot ulcer\n                    (DFU)","volume":"27","author":"N A Hamad","year":"2024","journal-title":"Pak J Biol Sci"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"111591","DOI":"10.1016\/j.diabres.2024.111591","article-title":"Association between antidepressants and the risk of diabetic foot ulcers and\n                    amputation in antidepressant-na\u00efve type 2 diabetes mellitus patients: A nested\n                    case-control study","volume":"209","author":"J Kim","year":"2024","journal-title":"Diabetes Res Clin Pract"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"e13531","DOI":"10.1111\/1753-0407.13531","article-title":"Factors associated with diabetic foot ulcers and lower limb amputations in type\n                    1 and type 2 diabetes supported by real-world data from the German\/Austrian DPV\n                    registry","volume":"16","author":"A J Eckert","year":"2024","journal-title":"J Diabetes"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1177\/0141076816688346","article-title":"Prevention and treatment of diabetic foot ulcers","volume":"110","author":"J Z Lim","year":"2017","journal-title":"J R Soc Med"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1001\/jama.2023.10578","article-title":"Diabetic foot ulcers: A Review","volume":"330","author":"D G Armstrong","year":"2023","journal-title":"JAMA"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"e14399","DOI":"10.1111\/iwj.14399","article-title":"The role of programmed cell death in diabetic foot ulcers","volume":"21","author":"J Li","year":"2023","journal-title":"Int Wound J"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"e15031","DOI":"10.1111\/dme.15031","article-title":"Bone marrow stromal cell-derived exosomal circular RNA improves diabetic foot\n                    ulcer wound healing by activating the nuclear factor erythroid 2-related factor\n                    2 pathway and inhibiting ferroptosis","volume":"40","author":"J Chen","year":"2023","journal-title":"Diabet Med"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1111\/iwj.14198","article-title":"Identification and verification of ferroptosis-related genes in diabetic foot\n                    using bioinformatics analysis","volume":"20","author":"X Wang","year":"2023","journal-title":"Int Wound J"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"944425","DOI":"10.3389\/fgene.2022.944425","article-title":"Revealing the novel ferroptosis-related therapeutic targets for diabetic foot\n                    ulcer based on the machine learning","volume":"13","author":"X Wang","year":"2022","journal-title":"Front Genet"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"e07897","DOI":"10.1016\/j.heliyon.2021.e07897","article-title":"Low-frequency vibration promotes AMPK-mediated glucose uptake in 3T3-L1\n                    adipocytes","volume":"7","author":"D Haba","year":"2021","journal-title":"Heliyon"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"660263","DOI":"10.3389\/fphys.2021.660263","article-title":"Liraglutide via activation of AMP-activated protein kinase-hypoxia inducible\n                    factor-1\u03b1-heme oxygenase-1 signaling promotes wound healing by preventing\n                    endothelial dysfunction in diabetic mice","volume":"12","author":"H Huang","year":"2021","journal-title":"Front Physiol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.2147\/DMSO.S299375","article-title":"Emodin ameliorates renal damage and podocyte injury in a rat model of diabetic\n                    nephropathy via regulating AMPK\/mTOR-mediated autophagy signaling pathway","volume":"14","author":"H Liu","year":"2021","journal-title":"Diabetes Metab Syndr Obes"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1517\/13543784.2014.922951","article-title":"AMP-activated protein kinase activators in diabetic ulcers: From animal studies\n                    to Phase II drugs under investigation","volume":"23","author":"J T Lin","year":"2014","journal-title":"Expert Opin Investig Drugs"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/MCO.0b013e3282fb7b76","article-title":"LKB1 and AMPK and the regulation of skeletal muscle metabolism","volume":"11","author":"H J Koh","year":"2008","journal-title":"Curr Opin Clin Nutr Metab Care"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1016\/j.bbrc.2020.10.040","article-title":"Klotho ameliorates diabetic nephropathy via LKB1-AMPK-PGC1\u03b1-mediated renal\n                    mitochondrial protection","volume":"534","author":"J Lee","year":"2021","journal-title":"Biochem Biophys Res Commun"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1080\/15548627.2021.1962681","article-title":"Vitamin D-VDR (vitamin D receptor) regulates defective autophagy in renal\n                    tubular epithelial cell in streptozotocin-induced diabetic mice via the AMPK\n                    pathway","volume":"18","author":"A Li","year":"2022","journal-title":"Autophagy"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"870","DOI":"10.3390\/diagnostics13050870","article-title":"Comprehensive analysis of prognosis and immune landscapes based on\n                    lipid-metabolism- and ferroptosis-associated signature in uterine corpus\n                    endometrial carcinoma","volume":"13","author":"P Yang","year":"2023","journal-title":"Diagnostics (Basel)"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"826","DOI":"10.7150\/ijbs.65938","article-title":"Neuraminidase 1 deficiency attenuates cardiac dysfunction, oxidative stress,\n                    fibrosis, inflammatory via AMPK-SIRT3 pathway in diabetic cardiomyopathy\n                    mice","volume":"18","author":"Z Guo","year":"2022","journal-title":"Int J Biol Sci"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"155952","DOI":"10.1016\/j.cyto.2022.155952","article-title":"Meteorin-like protein (Metrnl): A metabolic syndrome biomarker and an exercise\n                    mediator","volume":"157","author":"H Alizadeh","year":"2022","journal-title":"Cytokine"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1098570","DOI":"10.3389\/fimmu.2023.1098570","article-title":"Meteorin-like\/Metrnl, a novel secreted protein implicated in inflammation,\n                    immunology, and metabolism: A comprehensive review of preclinical and clinical\n                    studies","volume":"14","author":"Z Li","year":"2023","journal-title":"Front Immunol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0147-5","article-title":"METRNL attenuates lipid-induced inflammation and insulin resistance via AMPK or\n                    PPAR\u03b4-dependent pathways in skeletal muscle of mice","volume":"50","author":"T W Jung","year":"2018","journal-title":"Exp Mol Med"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1080\/08977194.2022.2032689","article-title":"Myokine-mediated exercise effects: The role of myokine meteorin-like hormone\n                    (Metrnl)","volume":"39","author":"H Alizadeh","year":"2021","journal-title":"Growth Factors"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"2326021","DOI":"10.1080\/10641963.2024.2326021","article-title":"Chicoric acid advanced PAQR3 ubiquitination to ameliorate ferroptosis in\n                    diabetes nephropathy through the relieving of the interaction between PAQR3 and\n                    P110\u03b1 pathway","volume":"46","author":"W Zhang","year":"2024","journal-title":"Clin Exp Hypertens"},{"key":"ref26","first-page":"3992","article-title":"Systematic understanding of the mechanism and effects of Arctigenin attenuates\n                    inflammation in dextran sulfate sodium-induced acute colitis through suppression\n                    of NLRP3 inflammasome by SIRT1","volume":"11","author":"Z Pu","year":"2019","journal-title":"Am J Transl Res"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"22588","DOI":"10.18632\/aging.203572","article-title":"GPR43 regulation of mitochondrial damage to alleviate inflammatory reaction in\n                    sepsis","volume":"13","author":"W Zhang","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.cmet.2020.11.018","article-title":"Apaf-1 Pyroptosome senses mitochondrial permeability transition","volume":"33","author":"W Xu","year":"2021","journal-title":"Cell Metab"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.bjps.2024.02.039","article-title":"Reconstruction of plantar forefoot in diabetic foot ulcers with microvascular\n                    tissue transfer using tunneled pedicle with dorsal anastomosis","volume":"91","author":"M Periasamy","year":"2024","journal-title":"J Plast Reconstr Aesthet Surg"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"265","DOI":"10.3390\/pharmaceutics16020265","article-title":"Dual glyoxalase-1 and \u03b2-klotho gene-activated scaffold reduces methylglyoxal and\n                    reprograms diabetic adipose-derived stem cells: Prospects in improved wound\n                    healing","volume":"16","author":"N Pang","year":"2024","journal-title":"Pharmaceutics"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"e3776","DOI":"10.1002\/dmrr.3776","article-title":"Diagnosis and treatment of diabetic foot ulcer complicated with lower extremity\n                    vasculopathy: Consensus recommendation from the Chinese Medical Association\n                    (CMA), Chinese Medical Doctor Association (CMDA)","volume":"40","author":"K Wang","year":"2024","journal-title":"Diabetes Metab Res Rev"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/wrr.13162","article-title":"The infected diabetic foot: Analysis of diabetic and non-diabetic foot\n                    infections","volume":"32","author":"L A Lavery","year":"2024","journal-title":"Wound Repair Regen"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1111\/wrr.13164","article-title":"MRSA infection, re-infection and clinical outcomes in diabetic foot\n                    infections","volume":"32","author":"M A Suludere","year":"2024","journal-title":"Wound Repair Regen"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/nyas.13569","article-title":"Update on management of diabetic foot ulcers","volume":"1411","author":"E Everett","year":"2018","journal-title":"Ann N Y Acad Sci"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1056\/NEJMra1615439","article-title":"Diabetic foot ulcers and their recurrence","volume":"376","author":"D G Armstrong","year":"2017","journal-title":"N Engl J Med"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41413-024-00319-7","article-title":"A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: Superior delivery\n                    of curcumin and alleviation of diabetic osteoporosis","volume":"12","author":"Y Li","year":"2024","journal-title":"Bone Res"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/j.ajpath.2024.01.019","article-title":"Ferroptosis contributes to microvascular dysfunction in diabetic\n                    retinopathy","volume":"194","author":"Q Liu","year":"2024","journal-title":"Am J Pathol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"154931","DOI":"10.1016\/j.phymed.2023.154931","article-title":"San Huang Xiao Yan recipe modulates the HMGB1-mediated abnormal inflammatory\n                    microenvironment and ameliorates diabetic foot by activating the AMPK\/Nrf2\n                    signalling pathway","volume":"118","author":"Z Zhang","year":"2023","journal-title":"Phytomedicine"},{"key":"ref42","first-page":"3110854","article-title":"Tangshen decoction enhances podocytes autophagy to relieve diabetic nephropathy\n                    through modulation of p-AMPK\/p-ULK1 signaling","volume":"2022","author":"L Yan","year":"2022","journal-title":"Evid Based Complement Alternat Med"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"165610","DOI":"10.1016\/j.bbadis.2019.165610","article-title":"Metformin reduces TRPC6 expression through AMPK activation and modulates\n                    cytoskeleton dynamics in podocytes under diabetic conditions","volume":"1866","author":"M Szrejder","year":"2020","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jare.2022.10.014","article-title":"Metrnl ameliorates diabetic cardiomyopathy via inactivation of cGAS\/STING\n                    signaling dependent on LKB1\/AMPK\/ULK1-mediated autophagy","volume":"51","author":"Q B Lu","year":"2023","journal-title":"J Adv Res"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nrc2676","article-title":"The LKB1-AMPK pathway: Metabolism and growth control in tumour suppression","volume":"9","author":"D B Shackelford","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s13098-019-0504-0","article-title":"The effect of cassia seed extract on the regulation of the LKB1-AMPK-GLUT4\n                    signaling pathway in the skeletal muscle of diabetic rats to improve the insulin\n                    sensitivity of the skeletal muscle","volume":"11","author":"Q Y Wang","year":"2019","journal-title":"Diabetol Metab Syndr"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.3390\/cells11182897","article-title":"Downregulation of LKB1\/AMPK signaling in blood mononuclear cells is associated\n                    with the severity of Guillain-Barre syndrome","volume":"11","author":"V Paunovic","year":"2022","journal-title":"Cells"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"111498","DOI":"10.1016\/j.celrep.2022.111498","article-title":"Downregulation of hepatic ceruloplasmin ameliorates NAFLD via SCO1-AMPK-LKB1\n                    complex","volume":"41","author":"L Xie","year":"2022","journal-title":"Cell Rep"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1007\/s11596-020-2210-4","article-title":"Berberine inhibits gluconeogenesis in skeletal muscles and adipose tissues in\n                    streptozotocin-induced diabetic rats via LKB1-AMPK-TORC2 signaling pathway","volume":"40","author":"X H Xu","year":"2020","journal-title":"Curr Med Sci"}],"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2502-8712.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T23:52:18Z","timestamp":1741823538000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2502-8712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":45,"journal-issue":{"issue":"03","published-online":{"date-parts":[[2025,3,12]]},"published-print":{"date-parts":[[2025,3]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2502-8712","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"value":"0947-7349","type":"print"},{"value":"1439-3646","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3]]}}}