Fibroblasts from IPF explanted lungs have mitochondrial dysfunction and short telomeres leading to an increased senescence phenotype

Abstract

Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive disease of the elderly. However, the complete mechanisms involved in the disease are still not well understood. We studied human Lung Fibroblasts (hLF) isolated from normal controls as well as IPF explanted lungs, in an effort to get a better understanding of the role that fibroblasts play in the disease. Our results suggest that hLF from IPF individuals differ from their age-matched controls in morphology, as well as in mitochondrial function. Additionally, IPF hLF have less collagen expression compared to controls. TGF-β has a negative effect in proliferation and a nule effect in mitochondrial function in fibroblasts. All these findings, together with the detection of shorter telomeres are associated with an increase in the expression of p21, p53 and the activity of β-galactosidase, suggesting a higher senescence phenotype in IPF hLF.