The Endothelin A Receptor Mediates Fibrocyte Differentiation in Chronic Obstructive Asthma. The Involvement of Connective Tissue Growth Factor

Abstract

Our findings demonstrate for the first time that the ETAR pathway is vital for CTGF expression, which results in fibrocyte differentiation in COA, and suggests that an ETAR antagonist may be a potential antifibrotic agent in preventing the development of fibrosis in patients with COA.

RPTOR, a novel target of miR-155, elicits a fibrotic phenotype of cystic fibrosis lung epithelium by upregulating CTGF

“…CTGF, a fibrotic factor, has been reported to be upregulated in other inflammatory diseases such as COPD and asthma, promoting increased fibrogenesis and remodeling of the airway tract. 29,30 Earlier studies have shown that rapamycin increased CTGF expression via TGF-b signaling pathway in lung epithelial cells and lung fibroblasts. 28,35 These studies also support our finding that CTGF may play a role in CF lung fibrosis through elevated miR-155 expression and consequent suppression of RPTOR levels.…”

“…28 CTGF is induced by physical, chemical or biological external stimuli (such as mechanical stretch, hypoxia or inflammation), and activates fibroblasts for more collagen synthesis, which leads to fibrosis. 17,18 Even though CTGF expression is high in several respiratory diseases such as asthma and emphysema, 29,30 its role in CF has not been examined. Interestingly, we found that IB3-1 CF cells exhibited increased expression of CTGF compared to IB3-1/S9 control cells (Figs.…”

Fibrocyte trafficking in patients with chronic obstructive asthma and during an acute asthma exacerbation

“…[1][2][3][4] Fibrocytes are increased in peripheral blood 5,6 and the airway wall, 7 particularly in airway smooth muscle bundles of asthmatic patients. 8 The positive correlation between the number of a-smooth muscle actin-positive fibrocytes and the thickness of the lamina reticularis supports the notion that fibrocyte-derived myofibroblasts might contribute to the deposition of the subepithelial extracellular matrix.…”

Update in Asthma 2013

“…Furthermore, the effects of persistent asthma on fixed airway obstruction were synergistic with smoking, but only in those with atopy. The other studies focused on potential mechanisms of airway remodeling including fibrocytes and their products, connective tissue growth factor, and endothelin-1 (58), and markers of vascular perturbation in asthma, von Willebrand factor propeptide and P-selectin (60). In an interesting study of tissue remodeling in a condition closely related to asthma, Takabayashi and colleagues studied fibrin deposition in chronic rhinosinusitis (61).…”