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LKB1 deficiency upregulates RELM-α to drive airway goblet cell metaplasia.
Li, Yu; Zhang, Qiuyang; Li, Li; Hao, De; Cheng, Peiyong; Li, Kuan; Li, Xue; Wang, Jianhai; Wang, Qi; Du, Zhongchao; Ji, Hongbin; Chen, Huaiyong.
Afiliación
  • Li Y; Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin, 300350, China.
  • Zhang Q; Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Institute of Respiratory Diseases, Tianjin, China.
  • Li L; Department of Basic Medicine, Haihe Clinical School, Tianjin Medical University, Tianjin, China.
  • Hao; Tianjin Key Laboratory of Lung Regenerative Medicine, Tianjin, China.
  • Cheng P; Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin, 300350, China.
  • Li K; Key Research Laboratory for Infectious Disease Prevention for State Administration of Traditional Chinese Medicine, Tianjin Institute of Respiratory Diseases, Tianjin, China.
  • Li X; Department of Basic Medicine, Haihe Clinical School, Tianjin Medical University, Tianjin, China.
  • Wang J; Tianjin Key Laboratory of Lung Regenerative Medicine, Tianjin, China.
  • Wang Q; Department of Respiratory Medicine, Haihe Clinical School, Tianjin Medical University, Tianjin, China.
  • Du Z; Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin, 300350, China.
  • Ji H; Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin, 300350, China.
  • Chen H; Department of Basic Medicine, Haihe Hospital, Tianjin University, Tianjin, 300350, China.
Cell Mol Life Sci ; 79(1): 42, 2021 Dec 18.
Article en En | MEDLINE | ID: mdl-34921639
Targeting airway goblet cell metaplasia is a novel strategy that can potentially reduce the chronic obstructive pulmonary disease (COPD) symptoms. Tumor suppressor liver kinase B1 (LKB1) is an important regulator of the proliferation and differentiation of stem/progenitor cells. In this study, we report that LKB1 expression was downregulated in the lungs of patients with COPD and in those of cigarette smoke-exposed mice. Nkx2.1Cre; Lkb1f/f mice with conditional loss of Lkb1 in mouse lung epithelium displayed airway mucus hypersecretion and pulmonary macrophage infiltration. Single-cell transcriptomic analysis of the lung tissues from Nkx2.1Cre; Lkb1f/f mice further revealed that airway goblet cell differentiation was altered in the absence of LKB1. An organoid culture study demonstrated that Lkb1 deficiency in mouse airway (club) progenitor cells promoted the expression of FIZZ1/RELM-α, which drove airway goblet cell differentiation and pulmonary macrophage recruitment. Additionally, monocyte-derived macrophages in the lungs of Nkx2.1Cre; Lkb1f/f mice exhibited an alternatively activated M2 phenotype, while expressing RELM-α, which subsequently aggravated airway goblet cell metaplasia. Our findings suggest that the LKB1-mediated crosstalk between airway progenitor cells and macrophages regulates airway goblet cell metaplasia. Moreover, our data suggest that LKB1 agonists might serve as a potential therapeutic option to treat respiratory disorders associated with goblet cell metaplasia.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Caliciformes / Enfermedad Pulmonar Obstructiva Crónica / Proteínas Quinasas Activadas por AMP / Quinasas de la Proteína-Quinasa Activada por el AMP / Pulmón Límite: Animals / Humans Idioma: En Revista: Cell Mol Life Sci Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Caliciformes / Enfermedad Pulmonar Obstructiva Crónica / Proteínas Quinasas Activadas por AMP / Quinasas de la Proteína-Quinasa Activada por el AMP / Pulmón Límite: Animals / Humans Idioma: En Revista: Cell Mol Life Sci Asunto de la revista: BIOLOGIA MOLECULAR Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Suiza