title: ABCC6 deficiency is associated with activation of BMP signaling in liver and kidney.
abstract: Mutations in ABCC6 (ATP-binding cassette, subfamily C, member 6), an orphan transporter expressed in the liver, are the cause of pseudoxanthoma elasticum. Since ABCC6 was reported to affect matrix Gla protein (MGP), an inhibitor of bone morphogenetic proteins (BMPs), we studied BMP signaling and expression in various tissues of mice with and without functional ABCC. Enhanced BMP signaling was found in all examined tissues in the absence of ABCC6. Despite this, the expression of particular BMP proteins varied widely between tissues. Interestingly, the expression of most BMP proteins in the liver moved in the opposite direction to the same BMP proteins in kidneys in response to ABCC6 alterations. Thus, ABCC6 deficiency stimulates BMP signaling by acting on the expression of multiple BMPs.
authors.affiliation: Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, United States.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Blazquez-Medela
authors.affiliation: Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, United States.
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Guihard
authors.affiliation: Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, United States.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Yao
authors.affiliation: Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, United States.
authors.forename: Medet
authors.initials: M
authors.lastname: Jumabay
authors.affiliation: Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, United States ; Molecular Biology Institute, UCLA, United States.
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.affiliation: Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, United States ; Molecular Biology Institute, UCLA, United States.
authors.forename: Kristina I
authors.initials: KI
authors.lastname: Boström
authors.affiliation: Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1679, United States.
authors.forename: Yucheng
authors.initials: Y
authors.lastname: Yao
keywords: ABCC6, ATP-binding cassette, subfamily C, member 6; ATP-binding cassette sub-family C member 6 (ABCC6); BAEC, bovine aortic endothelial cells; BMP signaling; BMPs, bone morphogenetic proteins; Bone morphogenetic protein (BMP); Kidney; Liver; MGP, matrix Gla protein; Mouse; PXE, pseudoxanthoma elasticum; TGFβ, transforming growth factor beta