A Systematic Review of the Role of Dysfunctional Wound Healing in the Pathogenesis and Treatment of Idiopathic Pulmonary Fibrosis

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disorder showcasing an interaction between genetic predisposition and environmental risks. This usually involves the coaction of a mixture of cell types associated with abnormal wound healing, leading to structural distortion and loss of gas exchange function. IPF bears fatal prognosis due to respiratory failure, revealing a median survival of approximately 2 to 3 years. This review showcases the ongoing progress in understanding the complex pathophysiology of IPF and it highlights the latest potential clinical treatments. In IPF, various components of the immune system, particularly clotting cascade and shortened telomeres, are highly involved in disease pathobiology and progression. This review also illustrates two US Food and Drug Administration (FDA)-approved drugs, nintedanib (OFEV, Boehringer Ingelheim, Ingelheim am Rhein, Germany) and pirfenidone (Esbriet, Roche, Basel, Switzerland), that slow IPF progression, but unfortunately neither drug can reverse the course of the disease. Although the mechanisms underlying IPF remain poorly understood, this review unveils the past and current advances that encourage the detection of new IPF pathogenic pathways and the development of effective treatment methods for the near future.

Immunity-and-Matrix-Regulatory Cells Derived from Human Embryonic Stem Cells Safely and Effectively Treat Mouse Lung Injury and Fibrosis

“…The mouse BLM model is similar to human ALI/ARDS during the acute inflammatory phase. Although fibroblastic foci, alveolar epithelial type 2 cells hyperplasia and honeycombing lesions are reduced compared with those in humans, indicating that the reproduction of human ARDS is not complete in the mouse BLM model, injury to alveolar epithelial cells has been shown to be a common contributing factor to the pathogenesis of both human ARDS and BLM-induced mouse pulmonary injury 40,41 . To test the therapeutic efficacy of IMRCs in the BLM mouse model, the delivery route and schedule of administration (e.g.…”

Mitochondrial dysfunction in rat splenocytes following hemorrhagic shock

“…Some of these cytokines begin to appear as early as one hour after HI (34, 38, 50, 51). The initial inflammatory response is likely to be a repair process to balance cellular homeostasis, but persistent exacerbated inflammation following the initial insult contributes to organ dysfunction (5, 52, 53). Studies have also shown a depressed mitochondrial function in peripheral blood mononuclear cells following hemorrhagic shock (29).…”

Idiopathic pulmonary fibrosis: pathogenesis and management

“…Many chemokines, as TGF-β1, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), lead the process. If injury persists, or the ability to restore normality is impaired, the wound healing process will pass through an inflammatory phase, with increased levels of interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α), creating a biochemical environment leading to chronic abortive regeneration and tissue remodelling [ 34 ].…”

“…The tissue factor (TF)-dependent pathway is the most important in IPF pathogenesis, leading to a pro-coagulation state enhanced by increased levels of plasminogen activation-inhibitors as PAI1 and PAI2, active fibrinolysis inhibitors and protein C-inhibitors. The pro-coagulation environment reduces the degradation of extracellular matrix(ECM), resulting in a profibrotic effect, and inducing differentiation of fibroblasts into myofibroblasts via proteinase-activated receptors [ 34 , 35 ].…”