Testisin/Prss21 deficiency causes increased vascular permeability and a hemorrhagic phenotype during luteal angiogenesis

PloS One
Raymond J PeroutkaToni M Antalis

Abstract

Testisin (encoded by PRSS21) is a membrane anchored serine protease, which is tethered to the cell surface via a glycosylphosphatidylinositol (GPI)-anchor. While testisin is found in abundance in spermatozoa, it is also expressed in microvascular endothelial cells where its function is unknown. Here we identify testisin as a novel regulator of physiological hormone-induced angiogenesis and microvascular endothelial permeability. Using a murine model of rapid physiological angiogenesis during corpus luteal development in the ovary, we found that mice genetically deficient in testisin (Prss21-/-) show a substantially increased incidence of hemorrhages which are significantly more severe than in littermate control Prss21+/+ mice. This phenotype was associated with increased vascular leakiness, demonstrated by a greater accumulation of extravasated Evans blue dye in Prss21-/- ovaries. Live cell imaging of in vitro cultured microvascular endothelial cells depleted of testisin by siRNA knockdown revealed that loss of testisin markedly impaired reorganization and tubule-like formation on Matrigel basement membranes. Moreover testisin siRNA knockdown increased the paracellular permeability to FITC-albumin across endothelial cell monola...Continue Reading

References

Dec 1, 1992·The Journal of Investigative Dermatology·E W AdesT J Lawley
Mar 14, 1998·Experimental Cell Research·T L BachJ Martinez
Aug 18, 1999·Proceedings of the National Academy of Sciences of the United States of America·M CoradaE Dejana
Dec 22, 1999·Biochemical and Biophysical Research Communications·M InoueH Kido
Dec 9, 2000·Journal of the Society for Gynecologic Investigation·K ShigemasaT J O'Brien
Mar 22, 2001·The Journal of Biological Chemistry·G W WongR L Stevens
Jul 14, 2001·Arteriosclerosis, Thrombosis, and Vascular Biology·M S Pepper
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jen-Tsan ChiPatrick O Brown
Nov 14, 2003·Reproductive Biology and Endocrinology : RB&E·Hamish M Fraser, Christine Wulff
Jan 31, 2006·Experimental Cell Research·Roopali RoyMarsha A Moses
Mar 18, 2006·Thrombosis and Haemostasis·Gianfranco Bazzoni
May 25, 2007·Nature Reviews. Molecular Cell Biology·Ralf H Adams, Kari Alitalo
Sep 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael J AllinghamKeith Burridge
Oct 27, 2007·Biochimica Et Biophysica Acta·Yann Wallez, Philippe Huber
Feb 23, 2008·Angiogenesis·Janice A NagyHarold F Dvorak
Jun 21, 2008·Journal of Cell Science·Elisabetta DejanaMaria Grazia Lampugnani
Jul 18, 2008·Proceedings of the National Academy of Sciences of the United States of America·Frank KuhnertCalvin J Kuo
Aug 2, 2008·Nature Cell Biology·Julie Gavard, J Silvio Gutkind
Aug 30, 2008·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Misuzu YamashitaTadashi Baba
Aug 17, 2010·Current Opinion in Cell Biology·Elizabeth S Harris, W James Nelson
Jan 18, 2011·Progress in Molecular Biology and Translational Science·Toni M AntalisQingyu Wu
Jun 29, 2011·The International Journal of Developmental Biology·Domenico RibattiEnrico Crivellato
Jul 5, 2011·Annual Review of Cell and Developmental Biology·Roman Szabo, Thomas H Bugge
Aug 3, 2013·The Journal of Clinical Investigation·Jonathan WeltiPeter Carmeliet
Jan 17, 2014·Cell Adhesion & Migration·Julie Gavard
May 27, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Adama SidibéIsabelle Vilgrain
Oct 11, 2014·Scientific Reports·Hwai-Lee Wang, Ted Weita Lai
Feb 26, 2016·Annual Review of Pathology·Cindy Park-Windhol, Patricia A D'Amore
Dec 17, 2017·Microvascular Research·Sara ShoeibiShabnam Mohammadi
Apr 21, 2018·Science·Martin A SchwartzMichael Simons
Mar 27, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Gregory D ConwayToni M Antalis

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Methods Mentioned

BETA
Knockout
transfection
PCR
fluorescence microscopy
Assay
genotyping

Key Resources (RRID) Mentioned

MMRRC_060817

Software Mentioned

GraphPad Prism
Image J
Angiogenesis Analyzer
ImageJ
NIH ImageJ

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