{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:51:34Z","timestamp":1791251494444,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005565","name":"Johnson & Johnson Innovative Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005565","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Microvascular injury is a critical factor in the pathogenesis of diabetic nephropathy. Dysregulation in vascular endothelial growth factor\u2010A (VEGF\u2010A) signalling pathways exacerbates endothelial dysfunction, contributing to the progression of kidney disease. In this study, we tested whether selective blockade of VEGFR1, a decoy receptor that limits VEGF\u2010A availability for VEGFR2, could restore glomerular microvascular integrity in experimental diabetic nephropathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Male BTBR\n                      <jats:italic>ob\/ob<\/jats:italic>\n                      mice, a model of advanced Type 2 diabetic nephropathy, received chronic treatment with a monoclonal antibody blocking VEGFR1. Renal functional parameters, albuminuria and glomerular injury were evaluated and compared with mice treated with the ACE inhibitor lisinopril, used as standard therapy. Glomerular capillary density and filtration barrier integrity were assessed by immunofluorescence and ultrastructural analyses, including evaluation of endothelial fenestrations and glycocalyx preservation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>VEGFR1 blockade reduced glomerular hyperfiltration, albuminuria and glomerular injury. Unlike lisinopril, VEGFR1 inhibition prevented glomerular capillary rarefaction and preserved the integrity of glomerular filtration barrier components. Ultrastructural analyses demonstrated the maintenance of endothelial fenestrations and glycocalyx coverage, closely resembling that of wild\u2010type non\u2010diabetic mice. VEGFR1\u2010blocking antibody treatment increased circulating VEGF\u2010A and placental growth factor as well as renal VEGFR2 expression. These vascular outcomes translated into better animal survival, with no mortality among VEGFR1\u2010blocking antibody\u2010treated mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Selective VEGFR1 inhibition preserves the structure and function of the glomerular filtration barrier by targeting endothelial injury and ameliorates microvascular integrity. These findings identify VEGFR1 as a critical regulator of diabetic glomerular microvascular damage and suggest modulation of VEGF signalling as a potential therapeutic approach for diabetic nephropathy, for which current therapies provide imperfect renoprotection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71381","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:02:17Z","timestamp":1791248537000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Major Role of\n                    <scp>VEGFR1<\/scp>\n                    Blockade in Protecting Glomerular Endothelium in Experimental Diabetes"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1395-3172","authenticated-orcid":false,"given":"Monica","family":"Locatelli","sequence":"first","affiliation":[{"name":"Science and Technology Park Kilometro Rosso Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori  Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9806-6443","authenticated-orcid":false,"given":"Domenico","family":"Cerullo","sequence":"additional","affiliation":[{"name":"Science and Technology Park Kilometro Rosso Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori  Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7907-3047","authenticated-orcid":false,"given":"Daniela","family":"Corna","sequence":"additional","affiliation":[{"name":"Science and Technology Park Kilometro Rosso Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori  Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2092-7474","authenticated-orcid":false,"given":"Mauro","family":"Abbate","sequence":"additional","affiliation":[{"name":"Science and Technology Park Kilometro Rosso Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori  Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2208-9646","authenticated-orcid":false,"given":"Daniela","family":"Macconi","sequence":"additional","affiliation":[{"name":"Science and Technology Park Kilometro Rosso Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori  Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2282-871X","authenticated-orcid":false,"given":"Daniela","family":"Rottoli","sequence":"additional","affiliation":[{"name":"Science and Technology Park Kilometro Rosso Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori  Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6488-8913","authenticated-orcid":false,"given":"Sara","family":"Conti","sequence":"additional","affiliation":[{"name":"Science and Technology Park Kilometro Rosso Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori  Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1386-1868","authenticated-orcid":false,"given":"Cristina","family":"Zanchi","sequence":"additional","affiliation":[{"name":"Science and Technology Park Kilometro Rosso Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori  Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2373-8082","authenticated-orcid":false,"given":"Jingjun","family":"Li","sequence":"additional","affiliation":[{"name":"Johnson &amp; 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