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Receptor subtypes involved in lung fibroblast‐mediated collagen gel contraction stimulated by lysophosphatidic acid and serum
Author(s) -
Brady Stephanie A.,
Schulte Nancy A.,
Kassel Karen M.,
Rennard Stephen I.,
Toews Myron L.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.728.9
Subject(s) - lysophosphatidic acid , contraction (grammar) , agonist , receptor , stimulation , chemistry , endocrinology , medicine , fibroblast , fetal bovine serum , biochemistry , biology , cell , in vitro
Previous studies showed that the lipid mediator lysophosphatidic acid (LPA) stimulates lung fibroblast responses relevant to repair and remodeling, including contraction of collagen gels. Pharmacological probes were used to examine the LPA receptor subtypes involved in gel contraction and to test the contribution of LPA and its receptors to gel contraction stimulated by serum. HFL‐1 human fetal lung fibroblasts cast into collagen gels were cultured for 24 hr to develop tension. Gels were then released in the presence of LPA, serum, and/or LPA receptor‐selective drugs, and gel contraction was monitored over 6 hr. Stimulation by LPA was blocked by the LPA1+3 antagonist Ki16425. Gel contraction was stimulated by both the LPA1‐preferring agonist NAEPA and the LPA3‐preferring agonist OMPT, both of which were blocked by Ki16425. The LPA2‐preferring agonist FAP12 was much less effective. Stimulation by fetal bovine serum was similar to that by LPA and was also blocked by Ki16425. Thus activation of either LPA1 or LPA3 is necessary and sufficient for LPA stimulation of gel contraction, and LPA1 and/or LPA3 also mediate the gel contraction in response to serum. Supported by Nebraska INBRE grant NIH P20‐RR‐016469 .