ArticlePloS one2013
Hepatocyte growth factor activator inhibitor-1 is induced by bone morphogenetic proteins and regulates proliferation and cell fate of neural progenitor cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Membrane-Anchored Serine Protease Inhibitors: Physiological Functions, Mechanisms, and Roles in Cancer.International journal of molecular sciences · 2026Review
- Clinical Scale MSC-Derived Extracellular Vesicles Enhance Poststroke Neuroplasticity in Rodents and Non-Human Primates.Journal of extracellular vesicles · 2025Article
- Genetics of white color and iridophoroma in "Lemon Frost" leopard geckos.PLoS genetics · 2021Article
- HAI-1 is an independent predictor of lung cancer mortality and is required for M1 macrophage polarization.PloS one · 2021Article
- Immunophenotyping of Live Human Pluripotent Stem Cells by Flow Cytometry.Methods in molecular biology (Clifton, N.J.) · 2018Article
- The type II transmembrane serine protease matriptase cleaves the amyloid precursor protein and reduces its processing to β-amyloid peptide.The Journal of biological chemistry · 2017Article
- The crystal structure of a multidomain protease inhibitor (HAI-1) reveals the mechanism of its auto-inhibition.The Journal of biological chemistry · 2017Article
- Recombinant hepatocyte growth factor activator inhibitor 1: expression in Drosophila S2 cells, purification and crystallization.Acta crystallographica. Section F, Structural biology communications · 2017Article
- Broad integration of expression maps and co-expression networks compassing novel gene functions in the brain.Scientific reports · 2014Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeural progenitor cells (NPCs) in the developing neuroepithelium are regulated by intrinsic and extrinsic factors. There is evidence that NPCs form a self-supporting niche for cell maintenance and proliferation. However, molecular interactions and cell-cell contacts and the microenvironment within the neuroepithelium are largely unknown. We hypothesized that cellular proteases especially those associated with the cell surface of NPCs play a role in regulation of progenitor cells in the brain. METHODOLOGY/PRINCIPAL
findingsIn this work, we show that NPCs, isolated from striatal anlage of developing rat brain, express hepatocyte growth factor activator inhibitor-1 and -2 (HAI-1 and HAI-2) that are cell surface-linked serine protease inhibitors. In addition, radial glia cells derived from mouse embryonic stem cells also express HAI-1 and HAI-2. To study the functional significance of HAI-1 and HAI-2 in progenitor cells, we modulated their levels using expression plasmids or silencing RNA (siRNA) transfected into the NPCs. Data showed that overexpression of HAI-1 or HAI-2 decreased cell proliferation of cultured NPCs, whilst their siRNAs had opposite effects. HAI-1 also influenced NPC differentiation by increasing the number of glial fibrillary acidic protein (GFAP) expressing cells in the culture. Expression of HAI-1 in vivo decreased cell proliferation in developing neuroepithelium in E15 old animals and promoted astrocyte cell differentiation in neonatal animals. Studying the regulation of HAI-1, we observed that Bone morphogenetic protein-2 (BMP-2) and BMP-4 increased HAI-1 levels in the NPCs. Experiments using HAI-1-siRNA showed that these BMPs act on the NPCs partly in a HAI-1-dependent manner.
conclusionsThis study shows that the cell-surface serine protease inhibitors, HAI-1 and HAI-2 influence proliferation and cell fate of NPCs and their expression levels are linked to BMP signaling. Modulation of the levels and actions of HAI-1 in NPCs may be of a potential value in stem cell therapies in various brain diseases.
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