{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:42:34Z","timestamp":1785436954468,"version":"3.56.0"},"posted":{"date-parts":[[2026,3,2]]},"group-title":"Genetics","reference-count":4,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01 2DK105056-6, R56DK138158A1, R21DK131557A1, R03DK106451 and K08DK089015"],"award-info":[{"award-number":["R01 2DK105056-6, R56DK138158A1, R21DK131557A1, R03DK106451 and K08DK089015"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"name":"VA Merit","award":["I01BX006401A1"],"award-info":[{"award-number":["I01BX006401A1"]}]},{"name":"the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program","award":["W81XWH-19-1-0320"],"award-info":[{"award-number":["W81XWH-19-1-0320"]}]},{"name":"George M. O\u2019Brien Kidney Research Core Centers","award":["NIH P30 DK114857; NIH P30 DK079337"],"award-info":[{"award-number":["NIH P30 DK114857; NIH P30 DK079337"]}]},{"DOI":"10.13039\/100001463","name":"American Society of Nephrology","doi-asserted-by":"crossref","award":["Kidney Cure Ben J. Lipps Research Fellowship Program"],"award-info":[{"award-number":["Kidney Cure Ben J. Lipps Research Fellowship Program"]}],"id":[{"id":"10.13039\/100001463","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["Postdoctoral Fellowship"],"award-info":[{"award-number":["Postdoctoral Fellowship"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Autosomal dominant tubulointerstitial kidney disease due to uromodulin mutations (ADTKD-UMOD) is one of the leading hereditary kidney diseases. Currently there is no targeted treatment. To illuminate human relevance of mesencephalic astrocyte-derived neurotrophic factor (MANF)-based therapy, we have established patient induced pluripotent stem cell (iPSC)-derived kidney organoid model carrying UMOD p.H177-R185del, the leading mutation causing ADTKD. We have discovered that MANF can directly bind and repress ER calcium release channel IP3R1, thus enhancing AMPK-induced autophagy in a TRIB3-dependent manner. The therapeutic implication of this finding may well be extended to other protein misfolding diseases.<\/jats:p>","DOI":"10.64898\/2026.03.02.708095","type":"posted-content","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T03:35:12Z","timestamp":1772508912000},"source":"Crossref","is-referenced-by-count":0,"title":["MANF Clears Mutant Uromodulin in Human Kidney Organoids of Autosomal Dominant Tubulointerstitial Kidney Disease"],"prefix":"10.64898","author":[{"given":"Chenjian","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yili","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Materials Science and Engineering, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Tycksen","sequence":"additional","affiliation":[{"name":"Genome Technology Access Center, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayathri","family":"Kondepati","sequence":"additional","affiliation":[{"name":"Institute of Materials Science and Engineering, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendrah","family":"Kidd","sequence":"additional","affiliation":[{"name":"Department of Medicine, Wake Forest University, Winston-Salem, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiko","family":"Urano","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Lindahl","sequence":"additional","affiliation":[{"name":"University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Bleyer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Wake Forest University, Winston-Salem, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srikanth","family":"Singamaneni","sequence":"additional","affiliation":[{"name":"Institute of Materials Science and Engineering, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying Maggie","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO"},{"name":"St. Louis Veteran Affairs Medical Center, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"1","key":"2026030503000701000_2026.03.02.708095v1.1","doi-asserted-by":"crossref","first-page":"6493","DOI":"10.1038\/s41467-023-42154-0","article-title":"MANF stimulates autophagy and restores mitochondrial homeostasis to treat autosomal dominant tubulointerstitial kidney disease in mice","volume":"14","year":"2023","journal-title":"Nat Commun"},{"key":"2026030503000701000_2026.03.02.708095v1.2","unstructured":"Lake BB , et al. Cellular and Spatial Drivers of Unresolved Injury and Functional Decline in the Human Kidney. bioRxiv. 2025:2025.09.26.678707."},{"key":"2026030503000701000_2026.03.02.708095v1.3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1813580116"},{"issue":"5","key":"2026030503000701000_2026.03.02.708095v1.4","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/s41551-020-0547-4","article-title":"Ultrabright fluorescent nanoscale labels for the femtomolar detection of analytes with standard bioassays","volume":"4","year":"2020","journal-title":"Nat Biomed Eng"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.02.708095","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T11:00:24Z","timestamp":1772708424000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.03.02.708095"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,2]]},"references-count":4,"URL":"https:\/\/doi.org\/10.64898\/2026.03.02.708095","relation":{},"subject":[],"published":{"date-parts":[[2026,3,2]]},"subtype":"preprint"}}