THE ROLE OF CAVEOLIN1 IN THE MIDKINE-MEDIATED PATHOGENESIS OF LUNG FIBROSIS IN ARDS
CCCF ePoster library. Huh U. Oct 27, 2015; 117330; P72 Disclosure(s): CIHR
Ustina Jung-Eun Huh
Ustina Jung-Eun Huh
Login now to access Regular content available to all registered users.

You may also access this content "anytime, anywhere" with the Free MULTILEARNING App for iOS and Android
Abstract
Rate & Comment (0)
P72


Topic: Basic/Translational Science


THE ROLE OF CAVEOLIN1 IN THE MIDKINE-MEDIATED PATHOGENESIS OF LUNG FIBROSIS IN ARDS



Ustina Jung-Eun Huh, B. Han, A. Luo, J. Laffey, M. Liu, A. Slutsky, H. Zhang

Physiology, University of Toronto, Toronto, Canada | Anesthesia, St.Michael's Hospital, Toronto, Canada | Institute of Medical Science, University of Toronto, Toronto, Canada | Anesthesia, St.Michael's Hospital, Toronto, Canada | Thoracic Surgery Research, Toronto General Hospital, Toronto, Canada | Anesthesia, St.Michael's Hospital, Toronto, Canada | Anesthesia, St.Michael's Hospital, Toronto, Canada

Introduction: Midkine (MK) is a cytokine which we have previously shown to be upregulated in ARDS patients, and induces the upregulation of angiotensin-converting enzyme (ACE) expression in an in vitro model of ventilator-induced lung injury (VILI). We have also established that a transmembrane protein, Notch2, serves as the cell surface receptor for MK.

Objectives: In the present study, we investigated the molecule Caveolin1 (Cav1), an emerging regulator of the tumor microenvironment that has been recently implicated in the pathogenesis of VILI. We hypothesized that Cav1 is a key modulator in the MK-Notch2-ACE signaling pathway.

Methods:

Human lung epithelial cells were challenged in vitro with HCl or vehicle control followed by 20% elongation mechanical stretch for 48h. MK, Notch2, Cav1, and ACE protein expressions were assessed by Western blot. To determine the interaction of Notch2 and Cav1, human lung epithelial cell whole cell lysate were extracted for co-immunoprecipitation analyses. Additional analyses were performed for Cav1 and Notch1, 3, and 4 interactions.



Results:

Exposure to mechanical stretch for 48h in human lung epithelial cells showed increased expression of MK, ACE, Notch2, and a significant decrease in Cav1 expression. Co-immunoprecipitation analysis showed that Notch2 directly interacts with Cav1. Further analyses demonstrated that other Notch homologs Notch1, 3, and 4 did not interact with Cav1.



Conclusion:

Activation of the MK-Notch2-Cav1-ACE signaling pathway contributes to lung injury and remodeling. Thus, the MK pathway may be a potential therapeutic target in attenuating ARDS-associated lung fibrosis and may significantly reduce mortality.



References: 1. Zhang, R. et al. Mechanical stress induces lung fibrosis via midkine signaling pathway. American Journal of Respiratory and Critical Care Medicine epub (2015).
    This eLearning portal is powered by:
    This eLearning portal is powered by MULTIEPORTAL
Anonymous User Privacy Preferences

Strictly Necessary Cookies (Always Active)

MULTILEARNING platforms and tools hereinafter referred as “MLG SOFTWARE” are provided to you as pure educational platforms/services requiring cookies to operate. In the case of the MLG SOFTWARE, cookies are essential for the Platform to function properly for the provision of education. If these cookies are disabled, a large subset of the functionality provided by the Platform will either be unavailable or cease to work as expected. The MLG SOFTWARE do not capture non-essential activities such as menu items and listings you click on or pages viewed.


Performance Cookies

Performance cookies are used to analyse how visitors use a website in order to provide a better user experience.


Save Settings