ArticleCell reports2026
Loss of laminin-γ1 in pericytes impairs microvascular function and cognition.
Jingsong Ruan, Ava Nasrollahi, Cecilia Martin, Meisam Asgari, Andy Y Shih, Yao Yao
Abstract read
In one paragraphArticle in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
6 authors.
Jingsong RuanDepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Ava NasrollahiDepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Cecilia MartinCenter for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, USA.
Meisam AsgariDepartment of Medical Engineering, University of South Florida, Tampa, FL, USA.
Andy Y ShihCenter for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA; Department of Bioengineering, University of Washington, Seattle, WA, USA.
Yao YaoDepartment of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA. Electronic address: yao7@usf.edu.
Funding
Pericyte control of capillary perfusion in the Alzheimer's disease brainR01AG081840 · NIA · SEATTLE CHILDREN'S HOSPITAL · PI Andy Y Shih · 2023 to 2026
$3.4MPericyte structural plasticity and cerebrovascular healthR01AG062738 · NIA · SEATTLE CHILDREN'S HOSPITAL · PI SHIH, ANDY Y · 2020 to 2024
$3.0MFibroblast-derived laminin regulates blood-brain barrier integrity and fibroblast biology in hemorrhagic brainR01NS134134 · NINDS · UNIVERSITY OF SOUTH FLORIDA · PI Yao Yao · 2023 to 2026
$2.0MEndothelial laminin in blood brain barrier regulationR01HL146574 · NHLBI · UNIVERSITY OF SOUTH FLORIDA · PI YAO, YAO · 2019 to 2023
$1.9MBrain Drain: In Vivo Optical Interrogation of Venular Function in Gray and White MatterR01AG077731 · NIA · SEATTLE CHILDREN'S HOSPITAL · PI Andy Y Shih · 2025 to 2026
$1.5MThe roles of pericyte-derived laminin in neurovascular function and neurodegenerationR01AG065345 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI YAO, YAO · 2024 to 2025
$1.2MMicroglial laminin repairs blood-brain barrier damage and modulates microglial activation in stroke brainR01NS143215 · NINDS · UNIVERSITY OF SOUTH FLORIDA · PI Yao Yao · 2026 to 2026
$589kBrain extracellular matrix changes during normal aging and in Alzheimer diseaseR21AG091884 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI YAO, YAO · 2025 to 2025
$413kNHLBI NIH HHS R01 HL146574NIA NIH HHS R01 AG062738NIA NIH HHS R01 AG065345NIA NIH HHS R01 AG077731NIA NIH HHS R01 AG081840NIA NIH HHS R21 AG091884NINDS NIH HHS R01 NS134134NINDS NIH HHS R01 NS143215
6 · The paper itselfAbstract
Blood-brain barrier (BBB) disruption correlates with lesion burden and cognitive dysfunction in cerebral small vessel disease (CSVD). Laminin, highly produced by pericytes in the brain, maintains BBB integrity. However, it remains unclear if laminin dysregulation contributes to the pathogenesis of CSVD. Here, we show that mice lacking laminin-γ1 in pericytes, smooth muscle cells, and fibroblasts (PKO) develop age-dependent BBB disruption via both paracellular and transcellular mechanisms. In contrast, loss of laminin-γ1 in smooth muscle cells or fibroblasts fails to affect BBB integrity. In addition, the PKO mice exhibit pericyte loss, thickened basal lamina, increased brain stiffness, followed by brain clearance defect, synaptic loss, and cognitive impairment. Together, these results demonstrate that loss of pericytic laminin-γ1 induces progressive vascular dysfunction and several features of CSVD, including brain stiffness, synaptic loss, and cognitive impairment, highlighting a potential role of laminin-γ1 dysregulation in the pathogenesis of CSVD.
Indexed as
CognitionLamininMicrovesselsPericytesAnimalsBlood-Brain BarrierBrainCerebral Small Vessel DiseasesFibroblastsMiceMice, Inbred C57BLMice, KnockoutMyocytes, Smooth MuscleLamininlaminin gamma 1blood-brain barriercerebral small vessel diseasecognitive impairmentCP: neurosciencelamininpericyte
Identifiers
PMID42658675
PMCPMC13657255
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