{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T22:49:51Z","timestamp":1784242191702,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Inserm, Sorbonne Universit\u00e9","award":["(AORC17)"],"award-info":[{"award-number":["(AORC17)"]}]},{"name":"Inserm, Sorbonne Universit\u00e9","award":["RAD16099LLA (HKL)"],"award-info":[{"award-number":["RAD16099LLA (HKL)"]}]},{"name":"\u201cFondation du Rein\u201d, France","award":["(AORC17)"],"award-info":[{"award-number":["(AORC17)"]}]},{"name":"\u201cFondation du Rein\u201d, France","award":["RAD16099LLA (HKL)"],"award-info":[{"award-number":["RAD16099LLA (HKL)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Focal segmental glomerulosclerosis (FSGS) is a major cause of end-stage renal disease and remains without specific treatment. To identify new events during FSGS progression, we used an experimental model of FSGS associated with nephroangiosclerosis in rats injected with L-NAME (N\u03c9-nitro-L-arginine methyl ester). After transcriptomic analysis we focused our study on the role of Isthmin-1 (ISM1, an anti-angiogenic protein involved in endothelial cell apoptosis. We studied the renal expression of ISM1 in L-NAME rats and other models of proteinuria, particularly at the glomerular level. In the L-NAME model, withdrawal of the stimulus partially restored basal ISM1 levels, along with an improvement in renal function. In other four animal models of proteinuria, ISM1 was overexpressed and localized in podocytes while the renal function was degraded. Together these facts suggest that the glomerular expression of ISM1 correlates directly with the progression-recovery of the disease. Further in vitro experiments demonstrated that ISM1 co-localized with its receptors GRP78 and integrin \u03b1v\u03b25 on podocytes. Treatment of human podocytes with low doses of recombinant ISM1 decreased cell viability and induced caspase activation. Stronger ISM1 stimuli in podocytes dropped mitochondrial membrane potential and induced nuclear translocation of apoptosis-inducing factor (AIF). Our results suggest that ISM1 participates in the progression of glomerular diseases and promotes podocyte apoptosis in two different complementary ways: one caspase-dependent and one caspase-independent associated with mitochondrial destabilization.<\/jats:p>","DOI":"10.3390\/ijms24032723","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T02:52:02Z","timestamp":1675219922000},"page":"2723","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Angiogenesis Inhibitor Isthmin-1 (ISM1) Is Overexpressed in Experimental Models of Glomerulopathy and Impairs the Viability of Podocytes"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0242-2114","authenticated-orcid":false,"given":"Virgilia","family":"Sahiri","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, UMR_S 1155, 75006 Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale UMR_S 1155, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Caron","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, UMR_S 1155, 75006 Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale UMR_S 1155, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Roger","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, UMR_S 1155, 75006 Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale UMR_S 1155, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Desterke","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, Facult\u00e9 de M\u00e9decine, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Universit\u00e9 Paris Saclay, INSERM UA\/09 UMR-S 935, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalil","family":"Ghachem","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, UMR_S 1155, 75006 Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale UMR_S 1155, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Mohamadou","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, UMR_S 1155, 75006 Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale UMR_S 1155, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Serre","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, UMR_S 1155, 75006 Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale UMR_S 1155, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niki","family":"Prakoura","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale UMR_S 1155, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soraya","family":"Fellahi","sequence":"additional","affiliation":[{"name":"Inserm UMR_S 938, Centre de Recherche Saint-Antoine, Institut Hospitalo-Universitaire de Cardio-M\u00e9tabolisme et Nutrition (ICAN), Sorbonne Universit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Placier","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, UMR_S 1155, 75006 Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale UMR_S 1155, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0265-7773","authenticated-orcid":false,"given":"Sahil","family":"Adriouch","sequence":"additional","affiliation":[{"name":"UNIROUEN, INSERM, U1234, Pathophysiology, Autoimmunity, Neuromuscular Diseases and Regenerative THERapies (PANTHER), Normandie University, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6657-7900","authenticated-orcid":false,"given":"Christos E.","family":"Chadjichristos","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, UMR_S 1155, 75006 Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale UMR_S 1155, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Chatziantoniou","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, UMR_S 1155, 75006 Paris, France"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale UMR_S 1155, 75020 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Kristian","family":"Lorenzo","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Saclay, INSERM UA\/09 UMR-S 935, 94800 Villejuif, France"},{"name":"Department of Nephrology, Bic\u00eatre Hospital, AP-HP, 94270 Le Kremlin-Bic\u00eatre, France"},{"name":"Universit\u00e9 Paris Saclay, INSERM UMR_S 1197, 94803 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Jacques","family":"Boffa","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, UMR_S 1155, 75006 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