{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:58:21Z","timestamp":1785412701412,"version":"3.56.0"},"posted":{"date-parts":[[2025,6,27]]},"group-title":"Cell Biology","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["7-21-JDF-020"],"award-info":[{"award-number":["7-21-JDF-020"]}],"id":[{"id":"https:\/\/ror.org\/04f6cgz95","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["F31 DK132926"],"award-info":[{"award-number":["F31 DK132926"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["5R01DK137221"],"award-info":[{"award-number":["5R01DK137221"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["P30-DK116073"],"award-info":[{"award-number":["P30-DK116073"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Breakthrough T1D","award":["3-SRA-2023-1417-S-B"],"award-info":[{"award-number":["3-SRA-2023-1417-S-B"]}]},{"name":"Breakthrough T1D","award":["3-SRA-2023-1367-S-B"],"award-info":[{"award-number":["3-SRA-2023-1367-S-B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Type 1 diabetes (T1D) is characterized by the immune-mediated destruction of insulin-producing \u03b2-cells in pancreatic islets. The peri-islet extracellular matrix (ECM) is a complex protein barrier that is lost in T1D, in part due to infiltrating immune cells. The contribution of stressed \u03b2-cells to ECM degradation during T1D remains unclear. To bridge this gap, we used 12\u201315-week-old NOD mice and pancreas sections from healthy, \u22652 autoantibody positive (Aab+), and recent onset T1D donors. We focused on MMP-3 due to its role in degrading type IV collagen (COL IV) in the peri-islet ECM. Treatment with proinflammatory cytokines or hyperglycemia increased MMP-3 gene expression and protein levels in mouse and human islets. In NOD pancreas sections, increased MMP-3 expression in \u03b2-cells correlates with loss of COL IV during insulitis and hyperglycemia; however, this was independent of insulitis score. We observed similar increases in MMP-3 and loss of COL IV in islets and exocrine tissue from Aab+ and recent onset T1D donors. These results suggest that stressed \u03b2-cells degrade the ECM during preclinical T1D, further weakening the peri-islet ECM barrier and facilitating islet infiltration and death. Inhibiting expression of MMP-3 may represent a novel treatment to prevent islet death in T1D.<\/jats:p>","DOI":"10.1101\/2025.06.25.661601","type":"posted-content","created":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T04:05:22Z","timestamp":1751083522000},"source":"Crossref","is-referenced-by-count":1,"title":["Stressed \u03b2-cells contribute to loss of peri-islet extracellular matrix in type 1 diabetes"],"prefix":"10.64898","author":[{"given":"Chelsea G.","family":"Johansen","sequence":"first","affiliation":[{"name":"Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenedee","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9834-9168","authenticated-orcid":false,"given":"Nikki L.","family":"Farnsworth","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, CO"},{"name":"Quantitative Biosciences & Engineering, Colorado School of Mines, Golden, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041210445286000_2025.06.25.661601v1.1","doi-asserted-by":"publisher","DOI":"10.3727\/096368909788237195"},{"key":"2026041210445286000_2025.06.25.661601v1.2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010245"},{"key":"2026041210445286000_2025.06.25.661601v1.3","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0432"},{"key":"2026041210445286000_2025.06.25.661601v1.4","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-1085-x"},{"key":"2026041210445286000_2025.06.25.661601v1.5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46177"},{"key":"2026041210445286000_2025.06.25.661601v1.6","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-014-0552-7"},{"key":"2026041210445286000_2025.06.25.661601v1.7","doi-asserted-by":"publisher","DOI":"10.1007\/s00776-006-1012-2"},{"key":"2026041210445286000_2025.06.25.661601v1.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176009"},{"key":"2026041210445286000_2025.06.25.661601v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2008.08.001"},{"key":"2026041210445286000_2025.06.25.661601v1.10","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.8.2034"},{"key":"2026041210445286000_2025.06.25.661601v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-814831-0.00022-1"},{"key":"2026041210445286000_2025.06.25.661601v1.12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI142242"},{"key":"2026041210445286000_2025.06.25.661601v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.13"},{"key":"2026041210445286000_2025.06.25.661601v1.14","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.suppl_2.S25"},{"key":"2026041210445286000_2025.06.25.661601v1.15","doi-asserted-by":"publisher","DOI":"10.3109\/14756366.2016.1161620"},{"key":"2026041210445286000_2025.06.25.661601v1.16","doi-asserted-by":"publisher","DOI":"10.1096\/fba.2021-00092"},{"key":"2026041210445286000_2025.06.25.661601v1.17","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-014-2056-9"},{"key":"2026041210445286000_2025.06.25.661601v1.18","doi-asserted-by":"crossref","unstructured":"Laronha, H. ; Caldeira, J. Structure and Function of Human Matrix Metalloproteinases. Cells 2020, 1\u201318.","DOI":"10.3390\/cells9051076"},{"key":"2026041210445286000_2025.06.25.661601v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2018.09.006"},{"key":"2026041210445286000_2025.06.25.661601v1.20","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.67.2.149"},{"key":"2026041210445286000_2025.06.25.661601v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(93)90054-S"},{"key":"2026041210445286000_2025.06.25.661601v1.22","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.65.2.137"},{"key":"2026041210445286000_2025.06.25.661601v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(93)90037-P"},{"key":"2026041210445286000_2025.06.25.661601v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-021-00129-z"},{"key":"2026041210445286000_2025.06.25.661601v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2013.02.007"},{"key":"2026041210445286000_2025.06.25.661601v1.26","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1131"},{"key":"2026041210445286000_2025.06.25.661601v1.27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2012.06826.x"},{"key":"2026041210445286000_2025.06.25.661601v1.28","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005058"},{"key":"2026041210445286000_2025.06.25.661601v1.29","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.752117"},{"key":"2026041210445286000_2025.06.25.661601v1.30","doi-asserted-by":"publisher","DOI":"10.1039\/d2ra07005g"},{"key":"2026041210445286000_2025.06.25.661601v1.31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.679506"},{"key":"2026041210445286000_2025.06.25.661601v1.32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115989"},{"key":"2026041210445286000_2025.06.25.661601v1.33","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1580205"},{"key":"2026041210445286000_2025.06.25.661601v1.34","doi-asserted-by":"publisher","DOI":"10.2337\/db20-0847"},{"key":"2026041210445286000_2025.06.25.661601v1.35","doi-asserted-by":"publisher","DOI":"10.18502\/ijph.v53i4.15562"},{"key":"2026041210445286000_2025.06.25.661601v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjps.2010.03.051"},{"issue":"1","key":"2026041210445286000_2025.06.25.661601v1.37","first-page":"25","article-title":"Immunohistochemical Study of the Pancreatic Basement Membrane in Non Obese Diabetic Mice (NOD) with Spontaneous Autoimmune Insulitis","volume":"35","year":"2003","journal-title":"J Submicrosc Cytol Pathol"},{"key":"2026041210445286000_2025.06.25.661601v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112913"},{"key":"2026041210445286000_2025.06.25.661601v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(00)00061-3"},{"key":"2026041210445286000_2025.06.25.661601v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2023.101678"},{"key":"2026041210445286000_2025.06.25.661601v1.41","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.248"},{"key":"2026041210445286000_2025.06.25.661601v1.42","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-007-0029-2"},{"key":"2026041210445286000_2025.06.25.661601v1.43","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.02-0874"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.06.25.661601","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:11:12Z","timestamp":1782277872000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.06.25.661601"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,27]]},"references-count":43,"URL":"https:\/\/doi.org\/10.1101\/2025.06.25.661601","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.3389\/fendo.2025.1675043","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,6,27]]},"subtype":"preprint"}}