Relaxin promotes matrix metalloproteinase-2 and decreases Wnt/beta-catenin expression in the neonatal porcine heart.
Relaxin (RLX), reported to play an important role in cardiovascular remodeling, is linked to activation of matrix metalloproteinases (MMPs). Interruption of the cardiac Wnt/beta-catenin signaling system is reported to have antihypertrophic effects. Thus, the objectives of this study were to determine the effects of RLX on the myocardial Wnt/beta-catenin signaling system and MMP expression in the postnatal day 2 (PND 2) porcine heart. Results showed that myocardial Wnt7a and Wnt4 gene expression at PND 2 decreased following treatment with RLX in vivo from birth, while there was no effect on Wnt5a expression. Immunoreactive myocardial beta-catenin protein was reduced in RLX-treated animals. Zymographic analysis of medium from RLX-treated heart explants showed an increase in pro-MMP-2 but not pro-MMP-9 activity. Western blot analysis indicated that RLX increased myocardial MMP-2 protein compared to controls. Data suggest that the RLX-induced decline in Wnt/beta-catenin expression at PND 2, together with increased MMP-2 activity, may be important for neonatal porcine cardiac remodeling.
Department of Animal Sciences, Rutgers University, New Brunswick, New Jersey 08901, USA.
Teh-Yuan
TY
Ho
Megan A
MA
Dilts
Frank F
FF
Bartol
Carol A
CA
Bagnell
D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D005786:Gene Expression Regulation / Q000187:drug effects*; D066298:In Vitro Techniques; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D012065:Relaxin / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060528:Wnt4 Protein; D051176:beta Catenin / Q000378:metabolism*
D051153:Wnt Proteins; D060528:Wnt4 Protein; D051176:beta Catenin; D012065:Relaxin; D020778:Matrix Metalloproteinase 2