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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 10
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 9, AUG 27 2019.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 17/17345-1 - Immunometabolism of inflammatory diseases: comparing the gene signatures of chikungunya-induced arthritis and obesity
Grantee:Thiago Dominguez Crespo Hirata
Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
FAPESP's process: 14/24162-2 - Analyses of the regulatory transcriptional mechanisms mediated by miRNAs in metabolic syndrome
Grantee:Thiago Dominguez Crespo Hirata
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)