Characterization of vitamin A-storing cells in mouse fibrous kidneys using Cygb/STAP as a marker of activated stellate cells.
The expression of the cytoglobin/stellate cell activation-associated protein (Cygb/STAP) was recently confirmed in all splanchnic vitamin A-storing cells--including hepatic stellate cells (HSCs)--in normal conditions. In the hepatic fibrous lesion, the expression of Cygb/STAP has been shown to be upregulated in activated HSCs and myofibroblasts (MFs), which have synthesized extracellular matrices. Furthermore, splanchnic vitamin A-storing cells have been reported to be distributed in the kidney. In this study, we clarify the contribution of vitamin A-storing cells to renal fibrosis by focusing on Cygb/ STAP. Adult mice were subjected to unilateral ureteral obstruction (UUO) and kidneys were harvested 1, 3, 7, and 10 days after UUO. Numbers of Cygb/STAP-immunopositive cells as well as Cygb/STAP mRNA 3 days after UUO (UUO day 3 kidney) increased. Vitamin A-autofluorescence was observed in intertubular spaces of controls but gradually declined in a time-dependent manner after UUO. Cygb/STAP+ cells were not completely identical with alpha-smooth muscle actin (alphaSMA)-positive cells in the control or UUO day 7 kidneys. Immunohistochemical analysis for Cygb/STAP and fibulin-2 (Fib), a specific marker for distinguishing MFs from activated HSCs, revealed that the number of Fib+STAP+ cells (MFs) and Fib-STAP+ cells (splanchnic vitamin A-storing cells) significantly increased in UUO day 3 and UUO day 7 kidneys compared with the controls. Our present findings support the concept that Cygb/STAP can be a unique marker for splanchnic fibroblast-like cells, namely the vitamin A-storing cell lineage, and suggest that splanchnic vitamin A-storing cells contribute to renal fibrogenesis in the obstructed kidney.
Kida
Yujiro
Y
Department of Anatomy II, School of Dental Medicine, Tsurumi University, Yokohama, Japan.
Asahina
Kinji
K
Inoue
Kouji
K
Kawada
Norifumi
N
Yoshizato
Katsutoshi
K
Wake
Kenjiro
K
Sato
Tetsuji
T
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D000078842:Cytoglobin; D005355:Fibrosis / Q000378:metabolism* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D005914:Globins / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000737:chemistry* / Q000378:metabolism; D007668:Kidney / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010544:Peroxidases / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D013153:Splanchnic Nerves / Q000166:cytology; D015854:Up-Regulation; D014801:Vitamin A / Q000378:metabolism* / Q000494:pharmacology