{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:28:07Z","timestamp":1786548487587,"version":"build-2736575974"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Collaborative Research Projects of Greater Bay Area Institute of Precision Medicine","award":["IPM2021C003"],"award-info":[{"award-number":["IPM2021C003"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170793"],"award-info":[{"award-number":["82170793"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Backgroud<\/jats:title>\n                    <jats:p>Nephrotic syndrome (NS) is a major cause of end-stage renal disease. Treating NS relies on immunosuppressants, which have numerous side effects. Therefore, there is an urgent need to identify effective and safe alternative treatments for NS. Angiopoietin-like protein 3 (ANGPTL3) exacerbates proteinuria, whereas interleukin (IL)-22 has a reparative effect on renal cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the present study, we developed a bifunctional anti-ANGPTL3\/IL-22 fusion protein and validated its efficacy in an adriamycin-induced nephropathy in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The fusion protein significantly decreased the urinary albumin-to-creatinine ratio, serum creatinine, blood urea nitrogen, and total cholesterol levels while increasing serum albumin levels. Pathological renal damage was also alleviated. These therapeutic effects were accompanied by the preservation of mitochondrial integrity, reduced apoptosis, and inhibited autophagy. Finally, we humanized the fusion protein to facilitate its potential clinical translation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In conclusion, our results revealed that the anti-ANGPTL3\/IL-22 bifunctional fusion protein ameliorates NS by protecting mitochondria, inhibiting apoptosis, and suppressing autophagy, highlighting a novel therapeutic approach for NS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/abt\/tbag031","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:14:27Z","timestamp":1781612067000},"page":"420-436","source":"Crossref","is-referenced-by-count":0,"title":["Anti-ANGPTL3 antibody and IL-22 fusion protein mitigate nephrotic syndrome via mitochondrial protection, anti-apoptosis, and autophagy suppression"],"prefix":"10.1093","volume":"9","author":[{"given":"Qianqian","family":"Ma","sequence":"first","affiliation":[{"name":"Neonatal Intensive Care Uite, Shandong Medical and Pharmaceutical University Hospital , Binzhou 256600 ,","place":["China"]},{"name":"Department of Nephrology, Children\u2019s Hospital of Fudan University, National Children\u2019s Medical Center , Shanghai 201102 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leilin","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Children\u2019s Hospital of Fudan University, National Children\u2019s Medical Center , Shanghai 201102 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangjun","family":"Jing","sequence":"additional","affiliation":[{"name":"iCareab Biotechnology Co. Ltd , Suzhou 215000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shandong Medical and Pharmaceutical University Hospital , Binzhou 256600 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaicheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University , Shanghai 201203 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fujie","family":"Wen","sequence":"additional","affiliation":[{"name":"First People's Hospital of Kashi No. 120 , Xinjiang 844000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Minhang Hospital, Fudan University , Shanghai 201199 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4305-9622","authenticated-orcid":false,"given":"Dianwen","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Biological Medicines & Shanghai Engineering Research Center of Immunotherapeutics, School of Pharmacy, Fudan University , Shanghai 201203 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2956-7436","authenticated-orcid":false,"given":"Hong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Children\u2019s Hospital of Fudan University, National Children\u2019s Medical Center , Shanghai 201102 ,","place":["China"]},{"name":"Greater Bay Area Institute of Precision Medicine , Guangzhou 510000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"2026081210262842900_ref1","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1056\/NEJMoa2314471","article-title":"Autoantibodies targeting nephrin in podocytopathies","volume":"391","author":"Hengel","year":"2024","journal-title":"N Engl J Med"},{"key":"2026081210262842900_ref2","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/S0140-6736(18)30536-1","article-title":"Idiopathic nephrotic syndrome in children","volume":"392","author":"Noone","year":"2018","journal-title":"Lancet"},{"key":"2026081210262842900_ref3","doi-asserted-by":"publisher","first-page":"115670","DOI":"10.1016\/j.biopha.2023.115670","article-title":"Podocyte injury of diabetic nephropathy: novel mechanism discovery and therapeutic prospects","volume":"168","author":"Li","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"2026081210262842900_ref4","doi-asserted-by":"publisher","first-page":"42764","DOI":"10.1038\/srep42764","article-title":"Autophagy protects against palmitic acid-induced apoptosis in podocytes in vitro","volume":"7","author":"Jiang","year":"2017","journal-title":"Sci Rep"},{"key":"2026081210262842900_ref5","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/nrneph.2014.233","article-title":"Autophagy failure and mitochondrial dysfunction in FSGS","volume":"11","author":"Carney","year":"2015","journal-title":"Nat Rev Nephrol"},{"key":"2026081210262842900_ref6","doi-asserted-by":"publisher","first-page":"32","DOI":"10.3389\/fped.2016.00032","article-title":"Pathology of podocytopathies causing nephrotic syndrome in children","volume":"4","author":"Ranganathan","year":"2016","journal-title":"Front Pediatr"},{"key":"2026081210262842900_ref7","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1038\/pr.2015.38","article-title":"A novel role of angiopoietin-like-3 associated with podocyte injury","volume":"77","author":"Liu","year":"2015","journal-title":"Pediatr Res"},{"key":"2026081210262842900_ref8","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/s12882-015-0034-4","article-title":"A vital role for Angptl3 in the PAN-induced podocyte loss by affecting detachment and apoptosis in vitro","volume":"16","author":"Dai","year":"2015","journal-title":"BMC Nephrol"},{"key":"2026081210262842900_ref9","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1038\/s41419-022-05313-7","article-title":"Anti-ANGPTL3-FLD monoclonal antibody treatment ameliorates podocyte lesions through attenuating mitochondrial damage","volume":"13","author":"Lv","year":"2022","journal-title":"Cell Death Dis"},{"key":"2026081210262842900_ref10","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1038\/s41419-023-06124-0","article-title":"Minnelide combined with anti-ANGPTL3-FLD monoclonal antibody completely protects mice with adriamycin nephropathy by promoting autophagy and inhibiting apoptosis","volume":"14","author":"Ji","year":"2023","journal-title":"Cell Death Dis"},{"key":"2026081210262842900_ref11","doi-asserted-by":"publisher","first-page":"E1249","DOI":"10.1073\/pnas.1717420115","article-title":"Increased thermogenesis by a noncanonical pathway in ANGPTL3\/8-deficient mice","volume":"115","author":"Banfi","year":"2018","journal-title":"Proc Natl Acad Sci"},{"key":"2026081210262842900_ref12","doi-asserted-by":"publisher","first-page":"2277","DOI":"10.3389\/fimmu.2019.02277","article-title":"Interleukin-22 attenuated renal tubular injury in aristolochic acid nephropathy via suppressing activation of NLRP3 inflammasome","volume":"10","author":"Wang","year":"2019","journal-title":"Front Immunol"},{"key":"2026081210262842900_ref13","doi-asserted-by":"publisher","first-page":"249","DOI":"10.7150\/ijbs.3967","article-title":"Interleukin-22 ameliorates cerulein-induced pancreatitis in mice by inhibiting the autophagic pathway","volume":"8","author":"Feng","year":"2012","journal-title":"Int J Biol Sci"},{"key":"2026081210262842900_ref14","doi-asserted-by":"publisher","first-page":"e324","DOI":"10.1002\/ctm2.324","article-title":"IL-22-mediated renal metabolic reprogramming via PFKFB3 to treat kidney injury","volume":"11","author":"Chen","year":"2021","journal-title":"Clin Transl Med"},{"key":"2026081210262842900_ref15","doi-asserted-by":"publisher","first-page":"1011442","DOI":"10.3389\/fimmu.2022.1011442","article-title":"A novel fusion protein consisting of anti-ANGPTL3 antibody and interleukin-22 ameliorates diabetic nephropathy in mice","volume":"13","author":"Ma","year":"2022","journal-title":"Front Immunol"},{"key":"2026081210262842900_ref16","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.4103\/1673-5374.280325","article-title":"Rac1 relieves neuronal injury induced by oxygenglucose deprivation and re-oxygenation via regulation of mitochondrial biogenesis and function","volume":"15","author":"Xia","year":"2020","journal-title":"Neural Regen Res"},{"key":"2026081210262842900_ref17","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1080\/20469047.2017.1374003","article-title":"Nephrotic syndrome in infants and children: pathophysiology and management","volume":"37","author":"Downie","year":"2017","journal-title":"Paediatr Int Child Health"},{"key":"2026081210262842900_ref18","doi-asserted-by":"publisher","first-page":"F520","DOI":"10.1152\/ajprenal.00570.2012","article-title":"Mitochondrial dysfunction is an early event in aldosterone-induced podocyte injury","volume":"305","author":"Su","year":"2013","journal-title":"Am J Physiol"},{"key":"2026081210262842900_ref19","doi-asserted-by":"publisher","first-page":"2484","DOI":"10.3390\/cells10092484","article-title":"The role of mitochondria in oocyte maturation","volume":"10","author":"Kirillova","year":"2021","journal-title":"Cells"},{"key":"2026081210262842900_ref20","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/s41581-020-00369-0","article-title":"Mitochondrial quality control in kidney injury and repair","volume":"17","author":"Tang","year":"2021","journal-title":"Nat Rev Nephrol"},{"key":"2026081210262842900_ref21","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1182\/blood-2018-01-829572","article-title":"Structure of an extended \u03b23 integrin","volume":"132","author":"Zhou","year":"2018","journal-title":"Blood"},{"key":"2026081210262842900_ref22","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.3389\/fphys.2020.00732","article-title":"The vicious cycle of renal lipotoxicity and mitochondrial dysfunction","volume":"11","author":"Ge","year":"2020","journal-title":"Front Physiol"},{"key":"2026081210262842900_ref23","doi-asserted-by":"publisher","first-page":"120753","DOI":"10.1016\/j.biomaterials.2021.120753","article-title":"Oral delivery of antioxidant enzymes for effective treatment of inflammatory disease","volume":"271","author":"Zeng","year":"2021","journal-title":"Biomaterials"},{"key":"2026081210262842900_ref24","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.biopha.2016.12.105","article-title":"Anti-oxidative effects of curcumin on immobilization-induced oxidative stress in rat brain, liver and kidney","volume":"87","author":"Samarghandian","year":"2017","journal-title":"Biomed Pharmacother"},{"key":"2026081210262842900_ref25","doi-asserted-by":"publisher","first-page":"2447","DOI":"10.1681\/ASN.2014060613","article-title":"Extracellular superoxide dismutase protects against proteinuric kidney disease","volume":"26","author":"Tan","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"2026081210262842900_ref26","doi-asserted-by":"publisher","first-page":"128839","DOI":"10.1016\/j.ijbiomac.2023.128839","article-title":"Exploring the chondroitin sulfate nanogel's potential in combating nephrotoxicity induced by cisplatin and doxorubicin\u2014an in-vivo study on rats","volume":"258","author":"Alqahtani","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"2026081210262842900_ref27","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1016\/0006-2952(94)90567-3","article-title":"Free radical modes of cytotoxicity of adriamycin\u00ae and streptonigrin","volume":"48","author":"DeGraff","year":"1994","journal-title":"Biochem Pharmacol"},{"key":"2026081210262842900_ref28","doi-asserted-by":"publisher","first-page":"2637","DOI":"10.1007\/s00253-022-11876-4","article-title":"Protective effects of interleukin-22 on oxalate-induced crystalline renal injury via alleviating mitochondrial damage and inflammatory response","volume":"106","author":"Gu","year":"2022","journal-title":"Appl Microbiol Biotechnol"},{"key":"2026081210262842900_ref29","doi-asserted-by":"publisher","first-page":"2131","DOI":"10.1038\/sj.ki.5000410","article-title":"The podocyte's response to injury: role in proteinuria and glomerulosclerosis","volume":"69","author":"Shankland","year":"2006","journal-title":"Kidney Int"},{"key":"2026081210262842900_ref30","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/j.envpol.2019.05.026","article-title":"Deoxynivalenol induced apoptosis and inflammation of IPEC-J2 cells by promoting ROS production","volume":"251","author":"Kang","year":"2019","journal-title":"Environ Pollut"},{"key":"2026081210262842900_ref31","doi-asserted-by":"publisher","first-page":"5829","DOI":"10.7150\/thno.44051","article-title":"Activation of TFEB-mediated autophagy by trehalose attenuates mitochondrial dysfunction in cisplatin-induced acute kidney injury","volume":"10","author":"Zhu","year":"2020","journal-title":"Theranostics"},{"key":"2026081210262842900_ref32","doi-asserted-by":"publisher","first-page":"5227","DOI":"10.1002\/ptr.7196","article-title":"A natural product of acteoside ameliorate kidney injury in diabetes db\/db mice and HK-2 cells via regulating NADPH\/oxidase-TGF-\u03b2\/Smad signaling pathway","volume":"35","author":"Wang","year":"2021","journal-title":"Phytother Res"},{"key":"2026081210262842900_ref33","doi-asserted-by":"publisher","first-page":"e22725","DOI":"10.1002\/jbt.22725","article-title":"Potential effect of adrenomedullin on metabolic and endocrinal dysfunctions in the experimentally induced polycystic ovary: targeting implication of endoplasmic reticulum stress","volume":"35","author":"El-Saka","year":"2021","journal-title":"J Biochem Mol Toxicol"},{"key":"2026081210262842900_ref34","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1681\/ASN.2013060611","article-title":"IL-22 ameliorates renal ischemia-reperfusion injury by targeting proximal tubule epithelium","volume":"25","author":"Xu","year":"2014","journal-title":"J Am Soc Nephrol"},{"key":"2026081210262842900_ref35","doi-asserted-by":"publisher","first-page":"100","DOI":"10.3390\/biom10010100","article-title":"Autophagy function and regulation in kidney disease","volume":"10","author":"Kaushal","year":"2020","journal-title":"Biomolecules"},{"key":"2026081210262842900_ref36","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-13-8871-2_28","article-title":"Cell apoptosis and autophagy in renal fibrosis","volume":"1165","author":"Zhao","journal-title":"Renal Fibrosis"},{"key":"2026081210262842900_ref37","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1080\/15548627.2019.1580512","article-title":"Podocytes and autophagy: a potential therapeutic target in lupus nephritis","volume":"15","author":"Zhou","year":"2019","journal-title":"Autophagy"},{"key":"2026081210262842900_ref38","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1007\/s00018-017-2639-1","article-title":"Autophagy in diabetic kidney disease: regulation, pathological role and therapeutic potential","volume":"75","author":"Yang","year":"2018","journal-title":"Cell Mol Life Sci"},{"key":"2026081210262842900_ref39","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.1089\/ars.2010.3488","article-title":"Oxidative stress stimulates autophagic flux during ischemia\/reperfusion","volume":"14","author":"Hariharan","year":"2011","journal-title":"Antioxid Redox Signal"},{"key":"2026081210262842900_ref40","doi-asserted-by":"publisher","first-page":"C203","DOI":"10.1152\/ajpcell.00097.2010","article-title":"Autophagy in health and disease. 5. Mitophagy as a way of life","volume":"299","author":"Gottlieb","year":"2010","journal-title":"Am J Physiol Cell Physiol"}],"container-title":["Antibody Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/abt\/advance-article-pdf\/doi\/10.1093\/abt\/tbag031\/68535424\/tbag031.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/abt\/article-pdf\/9\/3\/420\/68535424\/tbag031.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/abt\/article-pdf\/9\/3\/420\/68535424\/tbag031.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T14:27:39Z","timestamp":1786544859000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/abt\/article\/9\/3\/420\/8709018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,6,29]]}},"URL":"https:\/\/doi.org\/10.1093\/abt\/tbag031","relation":{},"ISSN":["2516-4236"],"issn-type":[{"value":"2516-4236","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7]]},"published":{"date-parts":[[2026,6,16]]}}}