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Role of EP2 receptors and cAMP in prostaglandin E 2 regulated expression of type I collagen α1, lysyl oxidase, and cyclooxygenase‐1 genes in human embryo lung fibroblasts
Author(s) -
Choung J.,
Taylor L.,
Thomas K.,
Zhou X.,
Kagan H.,
Yang X.,
Polgar P.
Publication year - 1998
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19981101)71:2<254::aid-jcb10>3.0.co;2-l
Subject(s) - forskolin , prostaglandin e2 receptor , prostaglandin e2 , lysyl oxidase , medicine , biology , receptor , endocrinology , microbiology and biotechnology , northern blot , agonist , messenger rna , chemistry , stimulation , biochemistry , gene , extracellular matrix
Abstract In a recent communication, we demonstrated that prostaglandin E 2 (PGE 2 ) lowers basal while it ablates interleukin‐1β( (IL‐1β) and transforming growth factor‐β (TGFβ) upregulated lysyl oxidase (LO) mRNA levels. Correspondingly, PGE 2 increases cyclooxygenase‐1 (COX1) mRNA in diploid, human embryo lung fibroblasts (IMR90) [Roy et al., 1996]. We now report that these actions by PGE 2 are routed through cAMP via the PGE 2 , EP2 receptor. Among the PGE 2 receptor types, the IMR90 predominantly express the EP2 mRNA. These cells also express EP3 and EP4 mRNA at comparatively low levels. Northern blot analyses show that 11‐deoxy PGE 1 , an EP2/EP4 agonist, emulates the action of PGE 2 . In a similar manner to PGE 2 , 11‐deoxy PGE 1 decreases basal and TGF‐β induced type I collagen α1 (COL) mRNA, basal and IL‐1β induced LO mRNA while it increases COX1 mRNA. Sulprostone, an EP3/EP1 agonist, has no effect on the expression of these three genes. Forskolin, an adenylate cyclase activator, acts in a very similar manner to PGE 2 or 11‐deoxy PGE 1 . It suppresses both basal and TGF‐β induced COL mRNA levels. Both PGE 2 and 11‐deoxy PGE 1 increase cAMP to a level comparable with forskolin. The role of the EP2 receptor in controlling collagen production is further underscored in the immortalized Rat‐1 fibroblasts, derived from Fischer rat embryos, which do not express detectable EP2 mRNA. In these cells, PGE 2 has little effect on COL mRNA level, whereas forskolin increases it. Furthermore, forskolin increases cAMP level in Rat‐1 cells, whereas PGE 2 does not. Overall, these results illustrate that much of the PGE 2 action on the expression of COL, LO, and COX1 genes is mediated through the EP2 receptor and a subsequent increase in intracellular cAMP. J. Cell. Biochem. 71:254–263, 1998. © 1998 Wiley‐Liss, Inc.