| Full text | |
| 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) |