TNF-α Sensitizes Normal and Fibrotic Human Lung Fibroblasts to Fas-Induced Apoptosis (original) (raw)

2006, American Journal of Respiratory Cell and Molecular Biology

Protein Tyrosine Phosphatase-N13 (PTPN13) Promotes Myofibroblast Resistance to Apoptosis in Idiopathic Pulmonary Fibrosis

American journal of respiratory and critical care medicine, 2018

Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic interstitial lung disease characterized by (myo)fibroblast accumulation and collagen deposition. Resistance to Fas-induced apoptosis is thought to facilitate (myo)fibroblast persistence in fibrotic lung tissues, by poorly understood mechanisms. We tested the hypothesis that protein tyrosine phosphatase PTPN13 is expressed by IPF lung (myo)fibroblasts, promotes their resistance to Fas-induced apoptosis and contributes to the development of pulmonary fibrosis. PTPN13 was localized in lung tissues from IPF patients and control subjects by immunohistochemical staining. Inhibition of PTPN13 function in primary IPF and normal lung (myo)fibroblasts was accomplished by: (i) down-regulation with TNF-α/IFN-γ, (ii) siRNA knockdown, or (iii) a cell permeable Fas:PTPN13 interaction inhibitory peptide. The role of PTPN13 in the development of pulmonary fibrosis was assessed in mice with genetic deficiency of PTP-BL, the murine ortholo...

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