Aldehyde metabolism governs resilience of mucociliary clearance to air pollution exposure

Shinjyo, Noriko; Kimura, Haruna; Yoshihara, Tomomi; Suzuki, Jun; Yamaguchi, Masaya; Kawabata, Shigetada; Okabe, Yasutaka

doi:https://doi.org/10.1172/JCI191276

Aldehyde metabolism governs resilience of mucociliary clearance to air pollution exposure

Shinjyo, Noriko; Kimura, Haruna; Yoshihara, Tomomi et al.

Journal of Clinical Investigation, 2025, 135(14), e191276

アクセス数:18件（2025-12-08 01:38 集計）

固定URL: https://hdl.handle.net/11094/102919

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タイトル	Aldehyde metabolism governs resilience of mucociliary clearance to air pollution exposure
著者	NRID 1000060794039 1000060794039 ORCID 0000-0003-4501-4513 0000-0003-4501-4513 researchmap permalink Noriko_Shinjyo Noriko_Shinjyo Scopus Author ID 6506391838 6506391838 著者名 Shinjyo, Noriko
	Scopus Author ID 59377626200 59377626200 著者名 Kimura, Haruna
	Scopus Author ID 58140535000 58140535000 著者名 Yoshihara, Tomomi
	NRID 1000030511894 1000030511894 著者名 Suzuki, Jun
	NRID 1000000714536 1000000714536 著者名 Yamaguchi, Masaya
	NRID 1000050273694 1000050273694 researchmap permalink read0185239 read0185239 Scopus Author ID 7201354003 7201354003 著者名 Kawabata, Shigetada
	NRID 1000050522124 1000050522124 ORCID 0000-0002-1913-7280 0000-0002-1913-7280 researchmap permalink 7000018117 7000018117 Scopus Author ID 36917266300 36917266300 著者名 Okabe, Yasutaka
内容	Shinjyo N., Kimura H., Yoshihara T., et al. Aldehyde metabolism governs resilience of mucociliary clearance to air pollution exposure. Journal of Clinical Investigation 135(14), e191276 (2025); https://doi.org/10.1172/JCI191276.
抄録	Air pollution is a serious environmental threat to public health; however, the molecular basis underlying its detrimental effects on respiratory fitness remains poorly understood. Here, we showed that exposure to particulate matter ≤ 2.5 μm (PM₂.₅), a substantial fraction of air pollutants, induced the generation of reactive aldehyde species in the airway. We identified aldehyde dehydrogenase 1A1 (ALDH1A1), which was selectively expressed in airway epithelium, as an enzyme responsible for detoxifying these reactive aldehyde species. Loss of ALDH1A1 function resulted in the accumulation of aldehyde adducts in the airway, which selectively impaired mucociliary clearance (MCC), a critical defense mechanism against respiratory pathogens. Thus, ALDH1A1-deficient mice pre-exposed to PM₂.₅ exhibited increased susceptibility to pneumonia. Conversely, pharmacological enhancement of ALDH1A1 activity promoted the restoration of MCC function. These findings elucidate the critical role of aldehyde metabolism in protecting against PM₂.₅ exposure, offering a potential target to mitigate the negative health consequences of air pollution.
出版者	American Society for Clinical Investigation
収録物名	Journal of Clinical Investigation
巻(号)	135(14)
ページ	e191276
刊行年月	2025-07-15
言語	英語
ハンドルURL	https://hdl.handle.net/11094/102919
PISSN	00219738
eISSN	15588238
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1172/JCI191276
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Journal of Clinical Investigation. 2025, 135(14), p. e191276
DC.title	Aldehyde metabolism governs resilience of mucociliary clearance to air pollution exposure
DC.creator	Shinjyo, Noriko
	Kimura, Haruna
	Yoshihara, Tomomi
	Suzuki, Jun
	Yamaguchi, Masaya
	Kawabata, Shigetada
	Okabe, Yasutaka
DC.publisher	American Society for Clinical Investigation
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-07-15
DC.identifier	https://doi.org/10.1172/JCI191276
DC.description	Shinjyo N., Kimura H., Yoshihara T., et al. Aldehyde metabolism governs resilience of mucociliary clearance to air pollution exposure. Journal of Clinical Investigation 135(14), e191276 (2025); https://doi.org/10.1172/JCI191276.
DCTERMS.abstract	Air pollution is a serious environmental threat to public health; however, the molecular basis underlying its detrimental effects on respiratory fitness remains poorly understood. Here, we showed that exposure to particulate matter ≤ 2.5 μm (PM₂.₅), a substantial fraction of air pollutants, induced the generation of reactive aldehyde species in the airway. We identified aldehyde dehydrogenase 1A1 (ALDH1A1), which was selectively expressed in airway epithelium, as an enzyme responsible for detoxifying these reactive aldehyde species. Loss of ALDH1A1 function resulted in the accumulation of aldehyde adducts in the airway, which selectively impaired mucociliary clearance (MCC), a critical defense mechanism against respiratory pathogens. Thus, ALDH1A1-deficient mice pre-exposed to PM₂.₅ exhibited increased susceptibility to pneumonia. Conversely, pharmacological enhancement of ALDH1A1 activity promoted the restoration of MCC function. These findings elucidate the critical role of aldehyde metabolism in protecting against PM₂.₅ exposure, offering a potential target to mitigate the negative health consequences of air pollution.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	102919
citation_title	Aldehyde metabolism governs resilience of mucociliary clearance to air pollution exposure
citation_author	Shinjyo, Noriko
	Kimura, Haruna
	Yoshihara, Tomomi
	Suzuki, Jun
	Yamaguchi, Masaya
	Kawabata, Shigetada
	Okabe, Yasutaka
citation_publisher	American Society for Clinical Investigation
citation_language	英語
citation_date	2025-07-15
citation_journal_title	Journal of Clinical Investigation
citation_volume	135
citation_issue	14
citation_firstpage	e191276
citation_doi	https://doi.org/10.1172/JCI191276
citation_public_url	https://hdl.handle.net/11094/102919

Aldehyde metabolism governs resilience of mucociliary clearance to air pollution exposure

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