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  • Peteri, Ulla KaisaUniversity of Helsinki,Univ Helsinki, Fac Med, Dept Physiol, POB 63, FI-00290 Helsinki, Finland. (author)

Urokinase plasminogen activator mediates changes in human astrocytes modeling fragile X syndrome

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-08-24
  • Wiley,2021

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:1d55cb01-cd36-4af2-a642-9f91319d8497
  • https://lup.lub.lu.se/record/1d55cb01-cd36-4af2-a642-9f91319d8497URI
  • https://doi.org/10.1002/glia.24080DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-469868URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • The function of astrocytes intertwines with the extracellular matrix, whose neuron and glial cell-derived components shape neuronal plasticity. Astrocyte abnormalities have been reported in the brain of the mouse model for fragile X syndrome (FXS), the most common cause of inherited intellectual disability, and a monogenic cause of autism spectrum disorder. We compared human FXS and control astrocytes generated from human induced pluripotent stem cells and we found increased expression of urokinase plasminogen activator (uPA), which modulates degradation of extracellular matrix. Several pathways associated with uPA and its receptor function were activated in FXS astrocytes. Levels of uPA were also increased in conditioned medium collected from FXS hiPSC-derived astrocyte cultures and correlated inversely with intracellular Ca2+ responses to activation of L-type voltage-gated calcium channels in human astrocytes. Increased uPA augmented neuronal phosphorylation of TrkB within the docking site for the phospholipase-Cγ1 (PLCγ1), indicating effects of uPA on neuronal plasticity. Gene expression changes during neuronal differentiation preceding astrogenesis likely contributed to properties of astrocytes with FXS-specific alterations that showed specificity by not affecting differentiation of adenosine triphosphate (ATP)-responsive astrocyte population. To conclude, our studies identified uPA as an important regulator of astrocyte function and demonstrated that increased uPA in human FXS astrocytes modulated astrocytic responses and neuronal plasticity.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Pitkonen, JuhoUniversity of Helsinki,Univ Helsinki, Fac Med, Dept Physiol, POB 63, FI-00290 Helsinki, Finland. (author)
  • de Toma, IlarioBarcelona Institute of Science and Technology,Barcelona Inst Sci & Technol, Syst Neurobiol Lab, Barcelona, Spain. (author)
  • Nieminen, OtsoUniversity of Helsinki,Univ Helsinki, Fac Med, Dept Physiol, POB 63, FI-00290 Helsinki, Finland. (author)
  • Utami, Kagistia HanaNational University of Singapore,Natl Univ Singapore NUS, Dept Physiol, Singapore, Singapore. (author)
  • Strandin, Tomas M.University of Helsinki,Univ Helsinki, Fac Med, Dept Virol, Helsinki, Finland. (author)
  • Corcoran, PádraicUppsala universitet,Uppsala University,Evolutionsbiologi,Systematisk biologi,Institutionen för medicinska vetenskaper(Swepub:uu)padco251 (author)
  • Roybon, LaurentLund University,Lunds universitet,Stamcellslaboratoriet för sjukdomsmodellering i det centrala nervsystemet,Forskargrupper vid Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,IPSC Laboratory for CNS Disease Modeling,Lund University Research Groups,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine,Lund Univ, BMC D10, Dept Expt Med Sci, iPSC Lab CNS Dis Modeling, Lund, Sweden.;Lund Univ, MultiPk, Lund, Sweden.;Lund Univ, Lund Stem Cell Ctr, Lund, Sweden.(Swepub:lu)mphy-lra (author)
  • Vaheri, AnttiUniversity of Helsinki,Univ Helsinki, Fac Med, Dept Virol, Helsinki, Finland. (author)
  • Ethell, IrynaUniversity of California, Riverside,Univ Calif Riverside, Biomed Sci, Sch Med, Riverside, CA 92521 USA. (author)
  • Casarotto, PlinioUniversity of Helsinki,Univ Helsinki, Neurosci Ctr, Helsinki, Finland. (author)
  • Pouladi, Mahmoud A.University of British Columbia,National University of Singapore,Natl Univ Singapore NUS, Dept Physiol, Singapore, Singapore.;Univ British Columbia, British Columbia Childrens Hosp, Dept Med Genet, Res Inst, Vancouver, BC, Canada. (author)
  • Castrén, Maija L.University of Helsinki,Univ Helsinki, Fac Med, Dept Physiol, POB 63, FI-00290 Helsinki, Finland. (author)
  • University of HelsinkiUniv Helsinki, Fac Med, Dept Physiol, POB 63, FI-00290 Helsinki, Finland. (creator_code:org_t)

Related titles

  • In:GLIA: Wiley69:12, s. 2947-29620894-14911098-1136

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