Syndecan-2 and Clinical Progression of Idiopathic Pulmonary Fibrosis

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

Investigators

Linked publications & trials

Abstract

The purpose of this proposal is to foster the scientific development and laboratory skills of Dr. Ivan Rosas in[unreadable] order that the candidate may become an independent investigator. The Pulmonary, Allergy and Critical Care[unreadable] Medicine Division at the University of Pittsburgh and it's Simmons Interstitial Lung Disease Center will[unreadable] provide the candidate with the ideal setting in which to test the hypothesis that clinical disease progression in[unreadable] IPF patients is associated with increases in Syndecan-2 expression and shedding.[unreadable] In order to identify candidate genes involved in the progression of IPF, the candidate performed microarray[unreadable] and targeted proteomic analysis of alveolar macrophages, broncho-alveolar lavage (BAL) and peripheral[unreadable] blood of IPF patients. He analyzed gene expression patterns in alveolar macrophages, and found that[unreadable] Syndecan-2 was upregulated. More importantly, the upregulation of Syndecan-2 correlated with disease[unreadable] severity in the study cohort. Syndecan-2, a member of the syndecan family of heparan-sulfate[unreadable] proteoglycans, can bind multiple chemokines, cytokines, growth factors and extracellular matrix proteins.[unreadable] Syndecan-2 can bind to these molecules as a membrane bound or shed protein. Although little is known[unreadable] about shedding and regulation of syndecans in human lung disease, they are known targets for matrix[unreadable] metallo-proteases (MMP's), which are highly abundant in the lungs of patients with IPF.[unreadable] The specific aims of this proposal are: 1 To determine whether SDC2 levels are indicative and predictive of[unreadable] disease development and progression. 2.To determine what MMP's, increased in IPF, regulate Syndecan-2[unreadable] shedding. 3.To determine the effects of syndecan expression and shedding on chemokine and growth factor[unreadable] bioavailability. The proposed research will offer insight into the role of Syndecan-2 in IPF disease[unreadable] progression. The knowledge obtained during the period of support will be the foundation for future studies[unreadable] determining the therapeutic potential of modulating levels of MMP's and heparan-sulfate proteoglycans in[unreadable] patients with IPF. Through the collaboration with Dr. Kaminski, Dr. Choi and a network of experienced[unreadable] researchers, the candidate will obtain the foundation for the development of an independent academic[unreadable] career.