Collagen 17A1 in the Urothelium Regulates Epithelial Cell Integrity and Local Immunologic Responses in Obstructive Uropathy

Namba, Takashi; Ichii, Osamu; Natsuga, Ken; Nakamura, Teppei; Otani, Yuki; Kon, Yasuhiro

Collagen 17A1 in the Urothelium Regulates Epithelial Cell Integrity and Local Immunologic Responses in Obstructive Uropathy

Namba, Takashi; Ichii, Osamu; Natsuga, Ken et al.

The American Journal of Pathology, 2024, 194(8), 1550-1570

Permalink : https://hdl.handle.net/2115/95869

このアイテムのアクセス数:105件（2026-07-23 05:08 集計）

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論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/95869
タイトル	Collagen 17A1 in the Urothelium Regulates Epithelial Cell Integrity and Local Immunologic Responses in Obstructive Uropathy
著者	Namba, Takashi ; Ichii, Osamu ; Natsuga, Ken ; Nakamura, Teppei ; Otani, Yuki ; Kon, Yasuhiro
著者名 Namba, Takashi
e-Rad_Researcher 60547769 著者名 Ichii, Osamu
著者名 Natsuga, Ken
e-Rad_Researcher 80786773 著者名 Nakamura, Teppei
e-Rad_Researcher 10909857 著者名 Otani, Yuki
e-Rad_Researcher 10178402 著者名 Kon, Yasuhiro
言語	英語
発行日	2024-07-24
出版者	Elsevier
収録物名	The American Journal of Pathology
巻(号)	194(8)
ページ	1550-1570
抄録	Collagen 17A1 (COL17A1), an epidermal hemidesmosome component, is ectopically induced in the urothelium of mouse and human renal pelvis (RP) in parallel with urinary tract-associated lymphoid structure development. Here, COL17A1 was induced in obstructive uropathy-prone ureter of humans and cats. To ascertain its function, murine urinary organs with unilateral ureteral obstruction (UUO) were analyzed during 1 week after surgery. One day after UUO, COL17A1 expression increased in urothelial cells of RP and ureter, and was positively correlated with renal tubulointerstitial lesions. A portion of RP where the smooth muscle layer from the ureter was interrupted was sensitive to urothelium deciduation and COL17A1 induction, showing urine leaked from the RP lumen into the parenchyma. After urine stimulation, cultured immune cells expressed Cxcl2, also up-regulated in CD11b & thorn; cells following COL17A1 stimulation. One day after UUO, CXCL2 & thorn; CD11b & thorn; cells infiltrated the urothelium-disrupted area. However, these numbers were significantly lower in Col17a1-deficient mice. COL17A1 & thorn; urothelial cells partially co-expressed cytokeratin-14, a progenitor cell marker for urothelium, whereas Col17a1-deficient mice had lower numbers of cytokeratin-14 & thorn; cells. Gene Ontology analysis revealed that expression of epithelial- and immune-associated genes was up-regulated and down-regulated, respectively, in the ureter of Col17a1-deficient mice 4 days after UUO. Thus, COL17A1 maintains urothelium integrity by regulating urothelial cell adhesion, proliferation, and differentiation, and activates local immune responses during obstructive uropathy in mammals.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 2024. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN	0002-9440
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.ajpath.2024.04.009