{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:24:55Z","timestamp":1792092295307,"version":"4.4.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>\n                    <jats:bold>Background<\/jats:bold>\n                    Laminin\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    5\n                    <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                    2\n                    <jats:italic toggle=\"yes\">\u03b3<\/jats:italic>\n                    1 (LM-521) is a major component of the GBM. Mutations in\n                    <jats:italic toggle=\"yes\">LAMB2<\/jats:italic>\n                    that prevent LM-521 synthesis and\/or secretion cause Pierson syndrome, a rare congenital nephrotic syndrome with diffuse mesangial sclerosis and ocular and neurologic defects. Because the GBM is uniquely accessible to plasma, which permeates endothelial cell fenestrae, we hypothesized that intravenous delivery of LM-521 could replace the missing LM-521 in the GBM of\n                    <jats:italic toggle=\"yes\">Lamb2<\/jats:italic>\n                    mutant mice and restore glomerular permselectivity.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods<\/jats:bold>\n                    We injected human LM-521 (hLM-521), a macromolecule of approximately 800 kD, into the retro-orbital sinus of\n                    <jats:italic toggle=\"yes\">Lamb2<\/jats:italic>\n                    \u2212\/\u2212 pups daily. Deposition of hLM-521 into the GBM was investigated by fluorescence microscopy. We assayed the effects of hLM-521 on glomerular permselectivity by urinalysis and the effects on podocytes by desmin immunostaining and ultrastructural analysis of podocyte architecture.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    Injected hLM-521 rapidly and stably accumulated in the GBM of all glomeruli. Super-resolution imaging showed that hLM-521 accumulated in the correct orientation in the GBM, primarily on the endothelial aspect. Treatment with hLM-521 greatly reduced the expression of the podocyte injury marker desmin and attenuated the foot process effacement observed in untreated pups. Moreover, treatment with hLM-521 delayed the onset of proteinuria but did not prevent nephrotic syndrome, perhaps due to its absence from the podocyte aspect of the GBM.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions<\/jats:bold>\n                    These studies show that GBM composition and function can be altered\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    vascular delivery of even very large proteins, which may advance therapeutic options for patients with abnormal GBM composition, whether genetic or acquired.\n                  <\/jats:p>","DOI":"10.1681\/asn.2017060690","type":"journal-article","created":{"date-parts":[[2018,2,22]],"date-time":"2018-02-22T10:56:31Z","timestamp":1519296991000},"page":"1426-1436","source":"Crossref","is-referenced-by-count":36,"title":["Laminin-521 Protein Therapy for Glomerular Basement Membrane and Podocyte Abnormalities in a Model of Pierson Syndrome"],"prefix":"10.1681","volume":"29","author":[{"given":"Meei-Hua","family":"Lin","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph B.","family":"Miller","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamato","family":"Kikkawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani Y.","family":"Suleiman","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Tryggvason","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School, Singapore, Singapore;"},{"name":"Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley L.","family":"Hodges","sequence":"additional","affiliation":[{"name":"Prothelia Inc., Milford, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey H.","family":"Miner","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,2,22]]},"reference":[{"key":"B1-20231016","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1007\/s00467-011-1785-1","article-title":"Glomerular basement membrane composition and the filtration barrier.","volume":"26","author":"Miner","year":"2011","journal-title":"Pediatr Nephrol"},{"key":"B2-20231016","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.yexcr.2012.02.031","article-title":"The glomerular basement membrane.","volume":"318","author":"Miner","year":"2012","journal-title":"Exp Cell Res"},{"key":"B3-20231016","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nrneph.2013.109","article-title":"The glomerular basement membrane as a barrier to albumin.","volume":"9","author":"Suh","year":"2013","journal-title":"Nat Rev Nephrol"},{"key":"B4-20231016","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1083\/jcb.201410017","article-title":"Review series: The cell biology of renal filtration.","volume":"209","author":"Scott","year":"2015","journal-title":"J Cell Biol"},{"key":"B5-20231016","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1126\/science.2349482","article-title":"Identification of mutations in the COL4A5 collagen gene in Alport syndrome.","volume":"248","author":"Barker","year":"1990","journal-title":"Science"},{"key":"B6-20231016","doi-asserted-by":"crossref","first-page":"26033","DOI":"10.1016\/S0021-9258(19)74270-7","article-title":"Type IV collagen: Structure, gene organization, and role in human diseases. 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