Increased fibroblast telomerase expression precedes myofibroblast α-smooth muscle actin expression in idiopathic pulmonary fibrosis

Abstract

OBJECTIVE:This study sought to identify the relationship between fibroblast telomerase expression, myofibroblasts, and telomerase-mediated regulatory signals in idiopathic pulmonary fibrosis.METHODS:Thirty-four surgical lung biopsies, which had been obtained from patients with idiopathic pulmonary fibrosis and histologically classified as usual interstitial pneumonia, were examined. Immunohistochemistry was used to evaluate fibroblast telomerase expression, myofibroblast α-smooth muscle actin expression and the tissue expression of interleukin-4, transforming growth factor-β, and basic fibroblast growth factor. The point-counting technique was used to quantify the expression of these markers in unaffected, collapsed, mural fibrosis, and honeycombing areas. The results were correlated to patient survival.RESULTS:Fibroblast telomerase expression and basic fibroblast growth factor tissue expression were higher in collapsed areas, whereas myofibroblast expression and interleukine-4 tissue expression were higher in areas of mural fibrosis. Transforming growth factor-β expression was higher in collapsed, mural fibrosis and honeycombing areas in comparison to unaffected areas. Positive correlations were found between basic fibroblast growth factor tissue expression and fibroblast telomerase expression and between interleukin-4 tissue expression and myofibroblast α-smooth muscle actin expression. Negative correlations were observed between interleukin-4 expression and basic fibroblast growth factor tissue expression in areas of mural fibrosis. Myofibroblast α-smooth muscle actin expression and interleukin-4 tissue expression in areas of mural fibrosis were negatively associated with patient survival.CONCLUSION:Fibroblast telomerase expression is higher in areas of early remodeling in lung tissues demonstrating typical interstitial pneumonia, whereas myofibroblast α-smooth muscle actin expression predominates in areas of late remodeling. These events seem to be regulated by basic fibroblast growth factor and interleukin-4 tissue expression, respectively.

Actin cytoskeleton redox proteome oxidation by cadmium

“…9B). The present studies support accumulating evidence (51,64,78) that the actin cytoskeleton function has a central role in lung function and disease. Thus the data highlight the importance of understanding effects of low-dose Cd on the actin cytoskeleton to help evaluate risks of environmental exposure.…”

Telomerase and Telomere Length in Pulmonary Fibrosis

“…Reduced fibrosis in TERT knockout (KO) mice can be restored by transplantation with wild-type (WT) bone marrow (BM), thus implicating the importance of a TERT-inducible, BM-derived cell during fibrosis (5,(8)(9)(10). A recent report revealed that fibroblast telomerase expression is higher in areas of early remodeling in lung tissue of idiopathic pulmonary fibrosis (IPF), which precedes the a-SMA expression that dominates in areas of late remodeling (11).…”

Radiation induced pulmonary fibrosis as a model of progressive fibrosis: Contributions of DNA damage, inflammatory response and cellular senescence genes

“…The question of whether restoration of the Th1/Th2 balance is a relevant treatment strategy in human IPF is complicated by the lack of available data, particularly during the onset of disease, as the majority of tissues from IPF patients are collected late in disease progression following a clinical diagnosis. While to date there is little evidence of prominent inflammation during early disease [107], increases in pro-fibrotic Th2 type cytokines, Il-4, Il-13, and Tgfβ, have been shown in tissue samples collected from IPF patients [58, 67]. This has led to clinical trials of several anti-Il-13 antibodies [7], although the results of these studies have yet to be published at the current time.…”