Tags

Type your tag names separated by a space and hit enter

Pathogenetic pathways and novel pharmacotherapeutic targets in idiopathic pulmonary fibrosis.
Pulm Pharmacol Ther 2007; 20(5):453-61PP

Abstract

Idiopathic pulmonary fibrosis (IPF) is a poorly understood disease that usually leads to death within 5 years of diagnosis. Despite our better understanding of IPF pathogenesis, the etiology and the precise cellular and molecular mechanisms involved are not well known. Current therapies are of unproven benefit. The aim of this review is to identify possible candidate pathways that might offer novel therapeutic targets changing the natural course of this disease. Current therapeutic approaches target at apoptosis, epithelial replacement, fibroblasts/myofibroblasts, procoagulant activity, growth factors production, angiogenesis, Th1 and Th2 cytokines and oxidative stress. Increased epithelial cells apoptosis can contribute to fibrosis, while on the other hand, decreased fibroblast or myofibroblast apoptosis promotes fibrosis. Recent findings support the notion that therapy directed at either inhibition of angiogenic or augmentation of angiostatic CXC chemokines may be a novel approach in the treatment of IPF. Additionally, there is little doubt that the development of novel therapeutic strategies for pulmonary fibrosis should target some profibrotic growth factors and key type II cytokines, such as inteleukin-13. Importantly, persistent activation of intra-alveolar procoagulant activity and subsequent abnormal fibrin turnover enhances a fibrotic response. Furthermore, increased procoagulant activity may interfere with fibrin accumulation and lack of activation of some matrix metalloproteinases responsible for an imbalance in matrix turnover. Finally, oxidative stress with increased production of oxidants in IPF is an additional mechanism proposed to explain epithelial cell apoptosis in this disease. The challenge of future targets for therapeutic intervention is to reconcile different pathogenetic pathways, and we strongly suspect that no single approach will be sufficient for a lethal disease with few therapeutic options.

Authors+Show Affiliations

Department of Thoracic Medicine, University Hospital, Medical School, University of Crete, Heraklion 71110 Crete, Greece.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

16516512

Citation

Antoniou, Katerina M., et al. "Pathogenetic Pathways and Novel Pharmacotherapeutic Targets in Idiopathic Pulmonary Fibrosis." Pulmonary Pharmacology & Therapeutics, vol. 20, no. 5, 2007, pp. 453-61.
Antoniou KM, Pataka A, Bouros D, et al. Pathogenetic pathways and novel pharmacotherapeutic targets in idiopathic pulmonary fibrosis. Pulm Pharmacol Ther. 2007;20(5):453-61.
Antoniou, K. M., Pataka, A., Bouros, D., & Siafakas, N. M. (2007). Pathogenetic pathways and novel pharmacotherapeutic targets in idiopathic pulmonary fibrosis. Pulmonary Pharmacology & Therapeutics, 20(5), pp. 453-61.
Antoniou KM, et al. Pathogenetic Pathways and Novel Pharmacotherapeutic Targets in Idiopathic Pulmonary Fibrosis. Pulm Pharmacol Ther. 2007;20(5):453-61. PubMed PMID: 16516512.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pathogenetic pathways and novel pharmacotherapeutic targets in idiopathic pulmonary fibrosis. AU - Antoniou,Katerina M, AU - Pataka,Athanasia, AU - Bouros,Demosthenes, AU - Siafakas,Nikolaos M, Y1 - 2006/03/03/ PY - 2005/11/16/received PY - 2006/01/18/revised PY - 2006/01/21/accepted PY - 2006/3/7/pubmed PY - 2007/12/28/medline PY - 2006/3/7/entrez SP - 453 EP - 61 JF - Pulmonary pharmacology & therapeutics JO - Pulm Pharmacol Ther VL - 20 IS - 5 N2 - Idiopathic pulmonary fibrosis (IPF) is a poorly understood disease that usually leads to death within 5 years of diagnosis. Despite our better understanding of IPF pathogenesis, the etiology and the precise cellular and molecular mechanisms involved are not well known. Current therapies are of unproven benefit. The aim of this review is to identify possible candidate pathways that might offer novel therapeutic targets changing the natural course of this disease. Current therapeutic approaches target at apoptosis, epithelial replacement, fibroblasts/myofibroblasts, procoagulant activity, growth factors production, angiogenesis, Th1 and Th2 cytokines and oxidative stress. Increased epithelial cells apoptosis can contribute to fibrosis, while on the other hand, decreased fibroblast or myofibroblast apoptosis promotes fibrosis. Recent findings support the notion that therapy directed at either inhibition of angiogenic or augmentation of angiostatic CXC chemokines may be a novel approach in the treatment of IPF. Additionally, there is little doubt that the development of novel therapeutic strategies for pulmonary fibrosis should target some profibrotic growth factors and key type II cytokines, such as inteleukin-13. Importantly, persistent activation of intra-alveolar procoagulant activity and subsequent abnormal fibrin turnover enhances a fibrotic response. Furthermore, increased procoagulant activity may interfere with fibrin accumulation and lack of activation of some matrix metalloproteinases responsible for an imbalance in matrix turnover. Finally, oxidative stress with increased production of oxidants in IPF is an additional mechanism proposed to explain epithelial cell apoptosis in this disease. The challenge of future targets for therapeutic intervention is to reconcile different pathogenetic pathways, and we strongly suspect that no single approach will be sufficient for a lethal disease with few therapeutic options. SN - 1094-5539 UR - https://www.unboundmedicine.com/medline/citation/16516512/Pathogenetic_pathways_and_novel_pharmacotherapeutic_targets_in_idiopathic_pulmonary_fibrosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1094-5539(06)00007-1 DB - PRIME DP - Unbound Medicine ER -