0
Diffuse Lung Disease |

Aging Alters the Unfolded Protein Response to Endoplasmic Reticulum Stress in Mouse Lung

Jessica Chia*, MD; Kenneth Schmader, MD; Paul Noble, MD
Author and Funding Information

Duke University Medical Center, Durham, NC


Chest. 2012;142(4_MeetingAbstracts):444A. doi:10.1378/chest.1390741
Text Size: A A A
Published online

Abstract

SESSION TYPE: ILD Posters

PRESENTED ON: Wednesday, October 24, 2012 at 01:30 PM - 02:30 PM

PURPOSE: Among the various interstitial lung diseases, idiopathic pulmonary fibrosis (IPF) is the most common, devastating, and fatal. A progressive condition of unknown etiology with a clear predilection for the elderly, IPF almost invariably ends in respiratory failure within five years of diagnosis. The limited understanding of IPF pathogenesis precludes the ability to provide effective treatment options. Evidence suggests that endoplasmic reticulum (ER) stress, protein misfolding, and the subsequent unfolded protein response (UPR) may represent a mechanism in the development of pulmonary fibrosis, as part of a dysfunctional repair process following lung injury. We therefore investigate whether the aging epithelium is more susceptible to ER stress and activation of the UPR.

METHODS: Using a murine model of pulmonary fibrosis and ER stress, we conduct in vivo and in vitro studies in young and aged C57Bl6 mice. Intrapulmonary tunicamycin is administered to induce ER stress. Protein expression of key components of the ER stress/UPR system is examined. Hydroxyproline assay and histology evaluate for the development of fibrosis.

RESULTS: In mouse whole lung and primary type 2 alveolar epithelial cells, tunicamycin reliably induces ER stress. Basal levels of protein chaperones are lower in naïve aged mice as compared to naïve young mice. Aged mice also display less BiP increase following ER stress. Basal levels of pro-apoptotic factors are higher in naïve aged mice and increase further following ER stress. Aged mice develop significantly more fibrosis in response to bleomycin as compared to their younger counterparts.

CONCLUSIONS: In mouse lung, aging alters the unfolded protein response to ER stress. Augmented lung fibrosis is seen in aging, which may be in part due to an altered ER stress/UPR pathway.

CLINICAL IMPLICATIONS: With enhanced understanding of the molecular and cellular aspects of pulmonary aging, and in particular the interaction between aging, pulmonary fibrosis, and ER stress, the ultimate goal is to develop effective therapies for, and thereby reduce mortality from, IPF.

DISCLOSURE: The following authors have nothing to disclose: Jessica Chia, Kenneth Schmader, Paul Noble

No Product/Research Disclosure Information

Duke University Medical Center, Durham, NC

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543