title: Prostaglandin F2α facilitates collagen synthesis in cardiac fibroblasts via an F-prostanoid receptor/protein kinase C/Rho kinase pathway independent of transforming growth factor β1.
abstract: Accumulation of collagen I and III in the myocardium is a prominent feature of interstitial fibrosis. Prostaglandin F(2α) (PGF(2α)) facilitates fibrosis by increasing collagen synthesis. However, the underlying mechanisms mediating the effect of PGF(2α) on collagen expression in cardiac fibroblasts are not yet fully elucidated. We measured the mRNA and protein levels of collagen I and III by quantitative real-time PCR and ELISA, respectively. Activation of signaling pathways was determined by western blot analysis. In primary rat cardiac fibroblasts, treatment with PGF(2α) stimulated both the mRNA and protein levels of collagen I and III, and pretreatment with the F-prostanoid (FP) receptor antagonist AL-8810, protein kinase C inhibitor LY-333531, and Rho kinase inhibitor Y-27632 significantly inhibited PGF(2α)-induced collagen I and III expression. FP receptor, protein kinase C, and Rho kinase were activated with PGF(2α) treatment. PGF(2α) may be an important regulator in the synthesis of collagen I and III via an FP receptor/protein kinase C/Rho kinase cascade in cardiac fibroblasts, which might be a new therapeutic target for myocardial fibrosis.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan 250012, PR China.
authors.forename: Wen-yuan
authors.initials: WY
authors.lastname: Ding
authors.forename: Yun
authors.initials: Y
authors.lastname: Ti
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.forename: Zhi-hao
authors.initials: ZH
authors.lastname: Wang
authors.forename: Guo-Lu
authors.initials: GL
authors.lastname: Xie
authors.forename: Yuan-yuan
authors.initials: YY
authors.lastname: Shang
authors.forename: Meng-xiong
authors.initials: MX
authors.lastname: Tang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhong
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003094:Collagen / Q000096:biosynthesis*; D015237:Dinoprost / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D011982:Receptors, Prostaglandin; D053773:Transforming Growth Factor beta1; D003094:Collagen; D015237:Dinoprost; D054460:rho-Associated Kinases; D011493:Protein Kinase C