Human soluble phospholipase A2 receptor is an inhibitor of the integrin-mediated cell migratory response to collagen-I

Am J Physiol Cell Physiol. 2018 Sep 1;315(3):C398-C408. doi: 10.1152/ajpcell.00239.2017. Epub 2018 May 23.

Abstract

Murine membrane-bound phospholipase A2 receptor 1 (PLA2R) is shed and released into plasma in a soluble form that retains all of the extracellular domains. Relatively little is known about human PLA2R. This study examined whether human soluble PLA2R has biological functions and whether soluble PLA2R exists in human plasma. Here, we showed that human recombinant soluble PLA2R (rsPLA2R) bound to collagen-I and inhibited interaction of collagen-I with the extracellular domain of integrin β1 on the cell surface of human embryonic kidney 293 (HEK293) cells. As a result, rsPLA2R suppressed integrin β1-mediated migratory responses of HEK293 cells to collagen-I in Boyden chamber experiments. Inhibition of phosphorylation of FAK Tyr397 was also observed. Similar results were obtained with experiments using soluble PLA2R released from HEK293 cells transfected with a construct encoding human soluble PLA2R. rsPLA2R lacking the fibronectin-like type II (FNII) domain had no inhibitory effects on cell responses to collagen-I, suggesting an important role of the FNII domain in the interaction of rsPLA2R with collagen-I. In addition, rsPLA2R suppressed the migratory response to collagen-IV and binding of collagen-IV to the cell surface of human podocytes that endogenously express membrane-bound, full-length PLA2R. Immunoprecipitation and Western blotting showed the existence of immunoreactive PLA2R in human plasma. In conclusion, human recombinant soluble PLA2R inhibits integrin β1-mediated cell responses to collagens. Further studies are warranted to elucidate whether immunoreactive PLA2R in human plasma has the same properties as rsPLA2R.

Keywords: collagen; integrin β1; phospholipase A2 receptor 1; soluble receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Line
  • Cell Membrane / metabolism
  • Cell Movement / physiology*
  • Chlorocebus aethiops
  • Collagen Type I / metabolism*
  • Collagen Type IV / metabolism
  • Fibronectins / metabolism
  • HEK293 Cells
  • Humans
  • Integrins / metabolism*
  • Phosphorylation / physiology
  • Podocytes / metabolism
  • Receptors, Phospholipase A2 / metabolism*

Substances

  • Collagen Type I
  • Collagen Type IV
  • Fibronectins
  • Integrins
  • PLA2R1 protein, human
  • Receptors, Phospholipase A2