Trpm7 Protein Contributes to Intercellular Junction Formation in Mouse Urothelium
別タイトル
TRPM7蛋白のマウス尿路上皮細胞間結合の形成への関与
著者
渡邊, 成樹
(Watanabe, Masaki)
上位タイトル
The Journal of biological chemistry.
Vol.290,
No.50
(2015.
12)
,p.29882-
29892
識別番号
DOI
10.1074/jbc.M115.667899
その他
PMID：26504086
博士論文情報
学位授与番号
10107A512
学位授与年月日
2017-06-30
学位名
博士（医学）
学位授与機関
旭川医科大学
抄録
Trpm7 is a divalent cation-permeable channel that has been reported to be involved in magnesium homeostasis as well as cellular adhesion and migration. We generated urothelium-specific Trpm7 knock-out (KO) mice to reveal the function of Trpm7 in vivo. A Trpm7 KO was induced by tamoxifen and was confirmed by genomic PCR and immunohistochemistry. By using patch clamp recordings in primary urothelial cells, we observed that Mg(2+)-inhibitable cation currents as well as acid-inducible currents were significantly smaller in Trpm7 KO urothelial cells than in cells from control mice. Assessment of voiding behavior indicated a significantly smaller voided volume in Trpm7 KO mice (mean voided volume 0.28 ± 0.08 g in KO mice and 0.36 ± 0.04 g in control mice, p < 0.05, n = 6-8). Histological analysis showed partial but substantial edema in the submucosal layer of Trpm7 KO mice, most likely due to inflammation. The expression of proinflammatory cytokines TNF-α and IL-1β was significantly higher in Trpm7 KO bladders than in controls. In transmission electron microscopic analysis, immature intercellular junctions were observed in Trpm7 KO urothelium but not in control mice. These results suggest that Trpm7 is involved in the formation of intercellular junctions in mouse urothelium. Immature intercellular junctions in Trpm7 knock-out mice might lead to a disruption of barrier function resulting in inflammation and hypersensitive bladder afferent nerves that may affect voiding behavior in vivo.
