Fine-tuning the ubiquitin-proteasome system to treat pulmonary fibrosis.

Fine-tuning the ubiquitin-proteasome system to treat pulmonary fibrosis.
Connect Tissue Res. 2018 Oct 22;:1-12
Authors: Roque W, Summer R, Romero F
Abstract
Idiopathic pulmonary fibrosis (IPF) is an extremely aggressive lung disease that develops almost exclusively in older individuals, carries a very poor prognosis, and lacks any truly effective therapies. The current conceptual model is that IPF develops because of an age-related decline in the ability of the lung epithelium to regenerate after injury, largely due to death or senescence of epithelial progenitor cells in the distal airways. This loss of regenerative capacity is thought to initiate a chronic and ineffective wound-healing response, characterized by persistent, low-grade lung inflammation and sustained production of collagen and other extracellular matrix materials. Despite recent advances in our understanding of IPF pathobiology, there remains a pressing need to further delineate underlying mechanisms to develop more effective therapies for this disease. In this review, we build the case that many of the manifestations of IPF result from a failure of cells to effectively manage their proteome. We propose that epithelial progenitor cells, as well as immune cells and fibroblasts, become functionally impaired, at least in part, because of an accumulation or a loss in the expression of various crucial proteins. Further, we propose that central to this defect is the dysreg...

Source: Connective Tissue Research - October 23, 2018 Category: Research Tags: Connect Tissue Res Source Type: research