Relaxin regulates fibrillin 2, but not fibrillin 1, mRNA and protein expression by human dermal fibroblasts and murine fetal skin.
Relaxin modulates connective tissue remodeling by altering matrix molecule expression. We have found that relaxin specifically inhibits a microfibril component, fibrillin 2 (FBN2), without affecting fibrillin 1 (FBN1). Human dermal fibroblasts (HDFs) grown or stimulated to overexpress fibrillin expression were used to show that relaxin specifically down-regulated FBN2 mRNA and protein levels. Continuous exposure of HDFs to relaxin (30ng/ml) significantly (P<0.05) decreased fibrillin 2 protein (40%) while FBN1 protein expression was unchanged. Our in vitro studies were confirmed using relaxin null mice whereby the absence of relaxin was associated with increased FBN2 mRNA and protein in fetal skin from pregnant relaxin knockout mice. The regulation of FBN2 expression may be associated with functional changes in elastic tissues during development and growth.
Samuel
Chrishan S
CS
Molecular Medicine Research Institute, 525 Del Rey Avenue, Suite B, Sunnyvale, CA 94085, USA. c.samuel@hfi.unimelb.edu.au
Sakai
Lynn Y
LY
Amento
Edward P
EP
D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics; D002478:Cells, Cultured; D017931:DNA Primers; D016326:Extracellular Matrix Proteins / Q000235:genetics; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D005786:Gene Expression Regulation; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D012065:Relaxin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012867:Skin / Q000196:embryology / Q000378:metabolism*; D054392:Adipokines
D002135:Calcium-Binding Proteins; D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins; D012333:RNA, Messenger; D012065:Relaxin; C000605722:FBN1 protein, human; D054392:Adipokines; C000605723:FBN2 protein, human; C000605724:Fbn1 protein, mouse; C000605728:Fbn2 protein, mouse