Your browser doesn't support javascript.
loading
The Elk1/MMP-9 axis regulates E-cadherin and occludin in ventilator-induced lung injury.
Tao, Zhao; Jie, Yan; Mingru, Zhang; Changping, Gu; Fan, Yang; Haifeng, Wu; Yuelan, Wang.
Afiliación
  • Tao Z; Department of Anesthesiology and Perioperative Medicine, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, No. 16766 Jingshi Road, Jinan, 250014, Shandong, China.
  • Jie Y; Department of Anesthesiology, People's Hospital of Rizhao, Jining Medical University, No. 126 Tai'an Road, Rizhao, 276826, Shandong, China.
  • Mingru Z; Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Anesthesia and Respiratory Critical Care Medicine, No. 16766 Jingshi Road, Jinan, 250014, Shandong, China.
  • Changping G; Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Anesthesia and Respiratory Critical Care Medicine, No. 16766 Jingshi Road, Jinan, 250014, Shandong, China.
  • Fan Y; Department of Anesthesiology and Perioperative Medicine, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, No. 16766 Jingshi Road, Jinan, 250014, Shandong, China.
  • Haifeng W; Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Anesthesia and Respiratory Critical Care Medicine, No. 16766 Jingshi Road, Jinan, 250014, Shandong, China.
  • Yuelan W; Department of Anesthesiology and Perioperative Medicine, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, No. 16766 Jingshi Road, Jinan, 250014, Shandong, China.
Respir Res ; 22(1): 233, 2021 Aug 23.
Article en En | MEDLINE | ID: mdl-34425812
BACKGROUND: Ventilator-induced lung injury (VILI) is a common complication in the treatment of respiratory diseases with high morbidity and mortality. ETS-domain containing protein (Elk1) and Matrix metalloproteinase (MMP) 9 are involved in VILI, but the roles have not been fully elucidated. This study examined the mechanisms of the activation of MMP-9 and Elk1 regulating barrier function in VILI in vitro and in vivo. METHODS: For the in vitro study, Mouse lung epithelial cells (MLE-12) were pre-treated with Elk1 siRNA or MMP-9 siRNA for 48 h prior to cyclic stretch at 20% for 4 h. For the in vivo study, C57BL/6 mice were pre-treated with Elk1 siRNA or MMP-9 siRNA for 72 h prior to 4 h of mechanical ventilation. The expressions of Elk1, MMP-9, Tissue inhibitor of metalloproteinase 1 (TIMP-1), E-cadherin, and occludin were measured by Western blotting. The intracellular distribution of E-cadherin and occludin was shown by immunofluorescence. The degree of pulmonary edema and lung injury were evaluated by Hematoxylin-eosin (HE) staining, lung injury scores, Wet/Dry (W/D) weight ratio, total cell counts, and Evans blue dye. RESULTS: 20% cyclic stretch and high tidal volume increases the expressions of Elk1, MMP-9, and TIMP-1, increases the ratio of MMP-9/TIMP-1, decreases the E-cadherin and occludin level. Elk1 siRNA or MMP-9 siRNA reverses the degradations of E-cadherin, occludin, and the ratio of MMP-9/TIMP-1 caused by cyclic stretch. Elk1 siRNA decreases the MMP-9 level with or not 20% cyclic stretch and high tidal volume. CONCLUSIONS: The results demonstrate mechanical stretch damages the tight junctions and aggravates the permeability in VILI, Elk1 plays an important role in affecting the tight junctions and permeability by regulating the balance of MMP-9 and TIMP-1, thus indicating the therapeutic potential of Elk1 to treat VILI.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Respiración Artificial / Cadherinas / Metaloproteinasa 9 de la Matriz / Proteína Elk-1 con Dominio ets / Lesión Pulmonar Inducida por Ventilación Mecánica / Ocludina Límite: Animals Idioma: En Revista: Respir Res Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Respiración Artificial / Cadherinas / Metaloproteinasa 9 de la Matriz / Proteína Elk-1 con Dominio ets / Lesión Pulmonar Inducida por Ventilación Mecánica / Ocludina Límite: Animals Idioma: En Revista: Respir Res Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido