SerpinB2 inhibits migration and promotes a resolution phase signature in large peritoneal macrophages

Autor(es)

Schroder, Wayne A. ^[1] ; Hirata, Thiago D. ^[2] ; Le, Thuy T. ^[1] ; Gardner, Joy ^[1] ; Boyle, Glen M. ^[1] ; Ellis, Jonathan ^[1] ; Nakayama, Eri ^[3] ; Pathirana, Dilan ^[1] ; Nakaya, Helder I. ^[2] ; Suhrbier, Andreas ^[1]

Afiliação do(s) autor(es)

^[1] QIMR Berghofer Med Res Inst, Brisbane, Qld 4029 - Australia

^[2] Univ Sao Paulo, Sch Pharmaceut Sci, Sao Paulo - Brazil

^[3] Natl Inst Infect Dis, Dept Virol 1, Tokyo 1628640 - Japan

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 9, AUG 27 2019.
• Citações Web of Science: 0

Resumo

SerpinB2 (plasminogen activator inhibitor type 2) has been called the ``undecided serpin{''} with no clear consensus on its physiological role, although it is well described as an inhibitor of urokinase plasminogen activator (uPA). In macrophages, pro-inflammatory stimuli usually induce SerpinB2; however, expression is constitutive in Gata6+ large peritoneal macrophages (LPM). Interrogation of expression data from human macrophages treated with a range of stimuli using a new bioinformatics tool, CEMiTool, suggested that SerpinB2 is most tightly co- and counter-regulated with genes associated with cell movement. Using LPM from SerpinB2(-/-) and SerpinB2(R)(380A) (active site mutant) mice, we show that migration on Matrigel was faster than for their wild-type controls. Confocal microscopy illustrated that SerpinB2 and F-actin staining overlapped in focal adhesions and lamellipodia. Genes associated with migration and extracellular matrix interactions were also identified by RNA-Seq analysis of migrating RPM from wild-type and SerpinB2(R)(380A) mice. Subsequent gene set enrichment analyses (GSEA) suggested SerpinB2 counter-regulates many Gata6-regulated genes associated with migration. These data argue that the role of SerpinB2 in macrophages is inhibition of uPA-mediated plasmin generation during cell migration. GSEA also suggested that SerpinB2 expression (likely via ensuing modulation of uPA-receptor/integrin signaling) promotes the adoption of a resolution phase signature. (AU)

• Processo FAPESP: 17/17345-1 - Imunometabolismo de doenças inflamatórias: comparação de assinaturas gênicas de artrite induzida por chikungunya e obesidade
• Beneficiário: Thiago Dominguez Crespo Hirata
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto
• Processo FAPESP: 14/24162-2 - Análise dos mecanismos regulatórios transcricionais mediados por microRNAs na síndrome metabólica
• Beneficiário: Thiago Dominguez Crespo Hirata
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto