{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ruan J"],"funding":["NIDDK NIH HHS","NIA NIH HHS","National Institute of Diabetes and Digestive and Kidney Diseases","NHLBI NIH HHS","National Heart, Lung, and Blood Institute","National Institute on Aging"],"pagination":["97"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9719645"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["19(1)"],"pubmed_abstract":["<h4>Background</h4>Unlike other proteins that exhibit a diffusion pattern after intracerebral injection, laminin displays a vascular pattern. It remains unclear if this unique vascular pattern is caused by laminin-receptor interaction or laminin self-assembly.<h4>Methods</h4>We compared the distribution of various wild-type laminin isoforms in the brain after intracerebral injection. To determine what causes the unique vascular pattern of laminin in the brain, laminin mutants with impaired receptor-binding and/or self-assembly activities and function-blocking antibodies to laminin receptors were used. In addition, the dynamics of laminin distribution and elimination were examined at multiple time points after intracerebral injection.<h4>Results</h4>We found that β2-containing laminins had higher affinity for the vessels compared to β1-containing laminins. In addition, laminin mutants lacking receptor-binding domains but not that lacking self-assembly capability showed substantially reduced vascular pattern. Consistent with this finding, dystroglycan (DAG1) function-blocking antibody significantly reduced the vascular pattern of wild-type laminin-111. Although failed to affect the vascular pattern when used alone, integrin-β1 function-blocking antibody further decreased the vascular pattern when combined with DAG1 antibody. EDTA, which impaired laminini-DAG1 interaction by chelating Ca<sup>2+</sup>, also attenuated the vascular pattern. Immunohistochemistry revealed that laminins were predominantly located in the perivascular space in capillaries and venules/veins but not arterioles/arteries. The time-course study showed that laminin mutants with impaired receptor-engaging activity were more efficiently eliminated from the brain compared to their wild-type counterparts. Concordantly, significantly higher levels of mutant laminins were detected in the cerebral-spinal fluid (CSF).<h4>Conclusions</h4>These findings suggest that intracerebrally injected laminins are enriched in the perivascular space in a receptor (DAG1/integrin)-dependent rather than self-assembly-dependent manner and eliminated from the brain mainly via the perivascular clearance system."],"journal":["Fluids and barriers of the CNS"],"pubmed_title":["Exogenous laminin exhibits a unique vascular pattern in the brain via binding to dystroglycan and integrins."],"pmcid":["PMC9719645"],"funding_grant_id":["R01 DK036425","R21 AG073862","RF1 AG065345","R21 AG064422","R01 HL146574","R01HL146574","RF1AG065345","R01DK036425"],"pubmed_authors":["Ruan J","Yao Y","McKee KK","Yurchenco PD"],"additional_accession":[]},"is_claimable":false,"name":"Exogenous laminin exhibits a unique vascular pattern in the brain via binding to dystroglycan and integrins.","description":"<h4>Background</h4>Unlike other proteins that exhibit a diffusion pattern after intracerebral injection, laminin displays a vascular pattern. It remains unclear if this unique vascular pattern is caused by laminin-receptor interaction or laminin self-assembly.<h4>Methods</h4>We compared the distribution of various wild-type laminin isoforms in the brain after intracerebral injection. To determine what causes the unique vascular pattern of laminin in the brain, laminin mutants with impaired receptor-binding and/or self-assembly activities and function-blocking antibodies to laminin receptors were used. In addition, the dynamics of laminin distribution and elimination were examined at multiple time points after intracerebral injection.<h4>Results</h4>We found that β2-containing laminins had higher affinity for the vessels compared to β1-containing laminins. In addition, laminin mutants lacking receptor-binding domains but not that lacking self-assembly capability showed substantially reduced vascular pattern. Consistent with this finding, dystroglycan (DAG1) function-blocking antibody significantly reduced the vascular pattern of wild-type laminin-111. Although failed to affect the vascular pattern when used alone, integrin-β1 function-blocking antibody further decreased the vascular pattern when combined with DAG1 antibody. EDTA, which impaired laminini-DAG1 interaction by chelating Ca<sup>2+</sup>, also attenuated the vascular pattern. Immunohistochemistry revealed that laminins were predominantly located in the perivascular space in capillaries and venules/veins but not arterioles/arteries. The time-course study showed that laminin mutants with impaired receptor-engaging activity were more efficiently eliminated from the brain compared to their wild-type counterparts. Concordantly, significantly higher levels of mutant laminins were detected in the cerebral-spinal fluid (CSF).<h4>Conclusions</h4>These findings suggest that intracerebrally injected laminins are enriched in the perivascular space in a receptor (DAG1/integrin)-dependent rather than self-assembly-dependent manner and eliminated from the brain mainly via the perivascular clearance system.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2025-04-04T13:46:19.617Z","creation":"2025-02-19T04:34:17.211Z"},"accession":"S-EPMC9719645","cross_references":{"pubmed":["36463265"],"doi":["10.1186/s12987-022-00396-y"]}}