Significant roles of the (pro)renin receptor in integrity of vascular smooth muscle cells.
The (pro)renin receptor ((P)RR) is known to play an important role in the pathogenesis of vascular complications in diabetes mellitus and hypertension through its function in activating the local renin-angiotensin system. Recent studies have shown that the (P)RR is an accessory protein of the vacuolar H(+)-ATPase, suggesting a more fundamental and developmental function. In this study, smooth muscle cell-specific (P)RR/Atp6ap2 conditional knockout mice were generated. Smooth muscle cell-specific ablation of the (P)RR resulted in nonatherogenic sclerosis in the abdominal aorta. The deletion of the (P)RR did not affect ambulatory blood pressure levels. In cultured murine vascular smooth muscle cells (VSMCs), ablation of the (P)RR suppressed the expression of the Vo subunit c of the vacuolar H(+)-ATPase and impaired the cell recycling system, leading to autophagic cell death. In addition, loss of the (P)RR in VSMCs induced the expression of monocyte chemotactic protein-1 and interleukin-6 mRNAs. These results suggest that the (P)RR is essential for cell survival and downregulation of vascular inflammation in murine VSMCs through maintaining normal function of the vacuolar H(+)-ATPase.
Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Asako
A
Kurauchi-Mito
1] Department of Medicine, Keio University School of Medicine, Tokyo, Japan [2] Department of Medicine II, Tokyo Women's Medical University, Tokyo, Japan.
Atsuhiro
A
Ichihara
Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Kanako
K
Bokuda
Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Mariyo
M
Sakoda
Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Kenichiro
K
Kinouchi
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
Tomonori
T
Yaguchi
Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
Taketo
T
Yamada
Department of Biochemistry, Faculty of Pharmaceutical Science, Doshisha Women's College, Kyoto, Japan.
Ge-Hong
GH
Sun-Wada
Division of Biological Sciences, Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan.
Yoh
Y
Wada
Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Hiroshi
H
Itoh
D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D015536:Down-Regulation; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*; D000093342:Prorenin Receptor
D011956:Receptors, Cell Surface; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; D000093342:Prorenin Receptor