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Upregulation of MUC5AC by VEGF in human primary bronchial epithelial cells: implications for asthma.
Kim, Sung-Ho; Pei, Qing-Mei; Jiang, Ping; Liu, Juan; Sun, Rong-Fei; Qian, Xue-Jiao; Liu, Jiang-Bo.
Afiliación
  • Kim SH; Department of Respiration, Tianjin First Central Hospital, Fukanglu-24, Nankaiqu, Tianjin, 300192, China. chenghao0726@hotmail.com.
  • Pei QM; Department of Radiology, Tianjin Hospital of Integrated Traditional Chinese and Western Medicine, Tianjin, China.
  • Jiang P; Department of Respiration, Tianjin First Central Hospital, Fukanglu-24, Nankaiqu, Tianjin, 300192, China.
  • Liu J; Department of Respiration, Tianjin First Central Hospital, Fukanglu-24, Nankaiqu, Tianjin, 300192, China.
  • Sun RF; Department of Respiration, Tianjin First Central Hospital, Fukanglu-24, Nankaiqu, Tianjin, 300192, China.
  • Qian XJ; Department of Respiration, Tianjin First Central Hospital, Fukanglu-24, Nankaiqu, Tianjin, 300192, China.
  • Liu JB; Department of Respiration, Tianjin First Central Hospital, Fukanglu-24, Nankaiqu, Tianjin, 300192, China.
Respir Res ; 20(1): 282, 2019 Dec 12.
Article en En | MEDLINE | ID: mdl-31831011
ABSTRACT

BACKGROUND:

Airway mucus hypersecretion is an important pathophysiological feature in asthma. Mucins are glycoproteins that are mainly responsible for the viscoelastic property of mucus, and MUC5AC is a major mucin glycoprotein that is overproduced in asthma. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodeling in asthmatics. Therefore, we sought to investigate the effect of VEGF on MUC5AC expression and study the underlying mechanisms.

METHODS:

In order to elucidate the precise mechanism underlying the effect of VEGF on MUC5AC expression, we tested the effects of VEGF on RhoA activation and the association of caveolin-1 and VEGFR2 in Primary Bronchial Epithelial Cells.

RESULTS:

VEGF up-regulated MUC5AC mRNA and protein levels in a dose- and time-dependent manner, and activated RhoA. Additionally, VEGF-induced MUC5AC expression and RhoA activation were enhanced by disrupting caveolae with cholesterol depletion and reversed by cholesterol repletion, and inhibited by a selective VEGF receptor 2 (VEGFR2) inhibitor SU1498. Furthermore, phospho-VEGFR2 expression was decreased via overexpression of caveolin-1. VEGF treatment reduced the association of caveolin-1 and VEGFR2.

CONCLUSION:

Collectively, our findings suggest that VEGF up-regulates MUC5AC expression and RhoA activation by interaction with VEGFR2, and this phenomenon was related with the association of caveolin-1 and VEGFR2. Further studies on these mechanisms are needed to facilitate the development of treatments for asthma.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Asma / Bronquios / Factor A de Crecimiento Endotelial Vascular / Células Epiteliales / Mucina 5AC Límite: Humans Idioma: En Revista: Respir Res Año: 2019 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Asma / Bronquios / Factor A de Crecimiento Endotelial Vascular / Células Epiteliales / Mucina 5AC Límite: Humans Idioma: En Revista: Respir Res Año: 2019 Tipo del documento: Article País de afiliación: China