Accession Number:

AD1111555

Title:

Large Noncoding RNAs as Therapeutic Targets in IPF

Descriptive Note:

[Technical Report, Annual Report]

Corporate Author:

YALE UNIVERSITY

Personal Author(s):

Report Date:

2019-10-01

Pagination or Media Count:

18

Abstract:

Our proposal focuses on the role of FENDRR, a developmentally regulated lincRNA that controls gene expression by affecting chromatin remodeling in Pulmonary fibrosis PF. PF is a condition in which the normal lung anatomy is replaced by a process of active remodeling, deposition of extracellular matrix ECM and accumulation of myofibroblasts. This condition can be idiopathic or secondary, but invariably associated with significant mortality and morbidity. In this project we test the hypothesis that FENDRR expression maintains fibroblasts differentiation status through its effects on chromatic organization, therefore when FENDRR expression is decreased, fibrosis is facilitated through persistence of myofibroblasts. We have made significant progress on our specific aims Specific aim 1 To determine the mechanisms by which FENDRR regulates fibroblast phenotypes - We identified now more the key epigenetic modifications that FENDRR is affecting the promoters of target genes to prevent fibrosis Specific aim 2 To determine the role of FENDRR in animal models of fibrosis - We have generated FENDRR knockout mice and demonstrate that they are more susceptible to fibrosis Specific Aim 3 To determine the implications of FENDRR down regulation in human lungs we confirmed the results and are now assessing target molecules.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

[A, Approved For Public Release]