ABSTRACT
Since chemerin is an adipocytokine whose concentration in blood increases in the subjects with various cardiac diseases, chemerin may be involved in pathogenesis of cardiac diseases. In the present study, we examined the effects of chemerin-9, an active fragment of chemerin, on functions of cardiac fibroblasts, which are involved in pathophysiology of cardiac diseases. Primary cardiac fibroblasts were enzymatically isolated from adult male Wistar rats. Migration of cardiac fibroblasts was measured by a Boyden chamber assay and a scratch assay. Phosphorylation of Akt and extracellular signal-regulated kinase (ERK) was measured by Western blotting. Reactive oxygen species (ROS) production was measured by 2',7'-dichlorodihydrofluoresein staining. Chemerin-9 significantly stimulated migration in cardiac fibroblasts. Chemerin-9 significantly stimulated phosphorylation of Akt and ERK as well as ROS production. An Akt pathway inhibitor, LY294002, an ERK pathway inhibitor, PD98059, an antagonist of chemokine-like receptor 1 (CMKLR1), 2-(α-Napththoyl) ethyltrimethylammonium iodide, or an antioxidant, N-acetyl-L-cysteine prevented the migration induced by chemerin-9. In summary, we for the first time revealed that chemerin-9 stimulates migration perhaps through the ROS-dependent activation of Akt and ERK via CMKLR1 in cardiac fibroblasts. It is proposed that chemerin plays a role in the pathogenesis of cardiac diseases.
Subject(s)
Cell Movement/drug effects , Chemokines/metabolism , Chemokines/pharmacology , Fibroblasts/drug effects , Acetylcysteine/pharmacology , Animals , Antioxidants/pharmacology , Chromones/pharmacology , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Extracellular Signal-Regulated MAP Kinases/metabolism , Flavonoids/pharmacology , Male , Morpholines/pharmacology , Myocardium/cytology , Naphthalenes/pharmacology , Phosphorylation/drug effects , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/metabolism , Quaternary Ammonium Compounds/pharmacology , Rats, Wistar , Reactive Oxygen Species/metabolism , Receptors, Chemokine/antagonists & inhibitors , Receptors, Chemokine/metabolismABSTRACT
The effects of a single subcutaneous or intramuscular injection of follicle-stimulating hormone (FSH) on follicular growth and expression of estrous behavior and its single subcutaneous administration on the number of corpora lutea (CL) and embryos were investigated in pigs. All four sows that were subcutaneously administered 5 AU FSH expressed normal estrus and had no ovarian cysts. Two of the four sows that were administered 5 AU FSH intramuscularly did not exhibit estrus, and another sow had a short estrus period. All four sows had ovarian cysts. The mean numbers of CL, embryos, and blastocysts following the subcutaneous administration of 5 AU FSH (16.8, 16.0, and 13.8, respectively) did not differ significantly from those for the control animals treated intramuscularly with 1000 IU equine chorionic gonadotropin (18.5, 16.5, and 14.3, respectively). In conclusion, embryo recovery was possible using a single subcutaneous administration of FSH.
