In:
American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 315, No. 3 ( 2018-09-01), p. C398-C408
Abstract:
Murine membrane-bound phospholipase A 2 receptor 1 (PLA 2 R) is shed and released into plasma in a soluble form that retains all of the extracellular domains. Relatively little is known about human PLA 2 R. This study examined whether human soluble PLA 2 R has biological functions and whether soluble PLA 2 R exists in human plasma. Here, we showed that human recombinant soluble PLA 2 R (rsPLA 2 R) 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, rsPLA 2 R 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 PLA 2 R released from HEK293 cells transfected with a construct encoding human soluble PLA 2 R. rsPLA 2 R 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 rsPLA 2 R with collagen-I. In addition, rsPLA 2 R 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 PLA 2 R. Immunoprecipitation and Western blotting showed the existence of immunoreactive PLA 2 R in human plasma. In conclusion, human recombinant soluble PLA 2 R inhibits integrin β1-mediated cell responses to collagens. Further studies are warranted to elucidate whether immunoreactive PLA 2 R in human plasma has the same properties as rsPLA 2 R.
Type of Medium:
Online Resource
ISSN:
0363-6143
,
1522-1563
DOI:
10.1152/ajpcell.00239.2017
Language:
English
Publisher:
American Physiological Society
Publication Date:
2018
detail.hit.zdb_id:
1477334-X
SSG:
12
