Cell reports · 2026
Lung epithelial endothelin-1 drives iron dysregulation and skeletal injury after SARS-CoV-2 infection.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Ошибки и ограничения
История · было → стало
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Ni Junguo, Au Man Ting, Tang Kaiming, Zhao Fangyi, Wang Wei, Zhang Lanlan, Zhou Bo, Zhu Lin, Lau Lawrence, Wang Xin, Tang Xiaodi, Kok Jie-Yi Koh, Young Lucy-May, Li Lin, Toh Yi-Chin, Wang Hantang, Liu Jun, Zhang Charlie Yuli, Lauwers Marianne, Luo Cuiting, Chan Jasper Fuk-Woo, Dong Cheng, Yuan Shuofeng, Wen Chunyi
Аннотация
Post-COVID musculoskeletal disorders are not uncommon; yet the mechanisms linking SARS-CoV-2 respiratory infection to skeletal injury remain unclear. Here, we identify a lung-joint axis in which elevated endothelin-1 (ET-1) in alveolar type Ⅱ cells (AT2) disrupts iron homeostasis and contributes to cartilage and growth plate injury after SARS-CoV-2 infection. Through scRNA sequencing and histopathological analysis of COVID-19 patients' and infected hamsters' lung and joint tissues, elevated ET-1 is linked to dysregulated iron homeostasis and iron accumulation. Mechanistically, genetically silencing ET-1 in lung epithelial cells attenuated viral spike-induced iron overload, while iron chelation improved the viability of chondrocytes in vitro. Therapeutically, the FDA-approved endothelin receptor antagonist, macitentan, protected infected hamsters from joint damage by reducing iron overload-associated chondrocyte dropout in both acute and subacute phase of infection in vivo. Our findings reveal the pathological ET-1 in lung-joint axis and highlight its receptors as therapeutic target for post-COVID skeletal sequelae.