Emerging evidence for endoplasmic reticulum stress in the pathogenesis of idiopathic pulmonary fibrosis

Abstract

Tanjore H, Blackwell TS, Lawson WE. Emerging evidence for endoplasmic reticulum stress in the pathogenesis of idiopathic pulmonary fibrosis.

Asbestos-induced Disruption of Calcium Homeostasis Induces Endoplasmic Reticulum Stress in Macrophages

“…Expression of the UPR in Macrophages in Vivo and ex VivoMost prior studies have documented ER stress with activation of the UPR in AECs or in fibroblasts using various disease models (3,32), whereas ER stress in alveolar macrophages from diseased lung has not been investigated. To evaluate ER stress in macrophages in vivo, C57BL/6 mice were exposed either to TiO 2 or chrysotile intratracheally and euthanized 21 days later.…”

“…Regarding fibrosis, most available evidence indicates that ER stress enhances the vulnerability of structural cells such as AECs and fibroblasts to fibrotic stimuli. In these studies, ER stress and UPR in AECs has been associated with herpesvirus infection (9,11), altered surfactant protein processing (9), expression of mutant surfactant proteins (9,10,34,35), apoptosis (8,11,12), epithelial-mesenchymal transitions (7), and induction of an inflammatory response (35) that ultimately leads to a profibrotic environment in lung tissue (2,3). To our knowledge, no studies have examined the UPR in macrophages in the setting of lung fibrosis.…”

“…A prototypical type of pulmonary fibrosis is caused by asbestos exposure, which is prevalent worldwide as at least 125 million are exposed to hazardous levels, including 1.3 million workers in the United States (1). The pathogenesis of asbestosis is not fully understood; however, recent evidence suggests that endoplasmic reticulum (ER) 2 stress and activation of the unfolded protein response (UPR) may contribute to fibrosis development in a variety of tissues, including the lung (2,3).…”

Basal cells of the human airways acquire mesenchymal traits in idiopathic pulmonary fibrosis and in culture

“…53 In the same bleomycin model with surfactant (SFTPC) mutated mice, the data also support the notion that ER stress can contribute to EMT in vivo. 54 Overexpression of mutant SFTPC in lung epithelial cell lines largely recapitulated the ER stress-induced EMT. 55 To argue against EMT as a driver of fibrosis, it has been shown as previously discussed that in the bleomcyininduced model multiple stromal cell populations contributed to the pulmonary fibrosis without any evidence for EMT.…”

Endoplasmic reticulum stress as a novel target to ameliorate epithelial-to-mesenchymal transition and apoptosis of human peritoneal mesothelial cells

“…20 The role of the UPR and ER stress has been demonstrated in idiopathic pulmonary fibrosis, as well as glomerulonephritis, diabetic nephropathy and drug-induced renal damage. 17,19,43,44 Despite ample evidence regarding the role of ER stress in organ fibrosis, the about ER stress and peritoneal fibrosis remain very limited. Previous studies revealed ultrastructural alterations of rough ER in the parietal peritoneum of patients on PD.…”