Regulation of COLx1(1), LO and COX-1 mRNA Expression by Prostaglandin E2 in Human Embryonic Fibroblasts, IMR-90.
Abstract
PGE2 decreases the synthesis of collagen and lysyl oxidase, key factors involved in fibrosis and tissue scarring. The mechanism by which PGE2 induces its inhibitory effect has been explored in human embryonic lung fibroblasts, IMR-90, and Rat-1 cells. In IMR-90, PGE2 limited COLalpha1(1) and LO mRNA expressions, but increased mRNA level of COX-1 which catalyzes PGE2 synthesis. Through Northern blot analysis, EP2, EP3 and EP4 receptor mRNAs were detected. Among these, EP2 mRNA expression was predominant, while EP3 and EP4 mRNAs were expressed in lesser degree with EP3 expression showing the least amount. EP1 receptor was not detected. Agonists, 11-deoxy PGE1 for EP2/EP4 and sulprostone for EP3/EP1, were used to determine the receptor type and possible signaling mechanism involved in mediating the PGE2 effect. 11-deoxy PGE1 demonstrated similar potency in limiting not only the basal but also TGF-beta and IL-1beta stimulated COLalpha1(1) and LO mRNA levels, respectively. Sulprostone showed no effect. Since EP2 and EP4 are known to generate cAMP, forskolin was used to examine this possibility. Forskolin showed similar results as PGE2 and 11-deoxy PGE1. However, forskolin with PGE2 showed greater inhibition of COLalpha1(1) mRNA level than either effector, alone. Rat-1 cells were used to further examine the importance of EP2 receptor. In contrast to IMR-90, PGE2 had no effect on COLalpha1(1) mRNA level, but forskolin increased it by almost 10-fold. Interestingly, only EP4 mRNA was detected in Rat-1 cells. These results suggest that EP2 is crucial in suppressing COLalpha1(1) and LO mRNA levels, subsequently limiting collagen deposition.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1998
- Accession Number
- ADA349483
Entities
People
- James K. Choung
Organizations
- Boston University