Abstract
BackgroundResistin-like molecule alpha or found in inflammatory zone protein (Fizz1) is increased in pulmonary epithelial cells and also in limited amounts by other lung cells during various lung injuries and fibrosis. However, the direct role of Fizz1 produced in the pulmonary epithelium has not been determined.MethodsFizz1 Transgenic mice (CCSP/Fizz1) were generated that overexpress Fizz1 in the lung epithelium under the control of a doxycycline (Dox) inducible lung epithelial cell specific promoter Scgb1a1 (Clara cell secretory protein, CCSP). Histology and FACS analysis of lung cells were used to identify the direct effects of Fizz1 in the transgenic mice (Dox treated) when compared with control (CCSP/-) mice. Intratracheal bleomycin sulfate or silica in saline and saline alone were used to study the role of Fizz1 during bleomycin- and silica-induced pulmonary fibrosis in CCSP/Fizz1 and CCSP/- mice. Weight change, pulmonary inflammation, and fibrosis were assessed 10 days post bleomycin or 28 days post silica challenge.ResultsWhen CCSP/Fizz1 mice were fed Dox food, elevated Fizz1 protein was detected in lung homogenates by western blot. Lungs of mice in which Fizz1 was induced in the epithelium contained increased lung cells staining for CD11c and F4/80 by FACS analysis consistent with increased dendritic cells however, no changes were observed in the percentage of interstitial macrophages compared to CCSP/- controls. No significant changes were found in the lung histology of CCSP/Fizz1 mice after up to 8 weeks of overexpression compared to CCSP/- controls. Overexpression of Fizz1 prior to challenge or following challenge with bleomycin or silica did not significantly alter airway inflammation or fibrosis compared to control mice.ConclusionsThe current study demonstrates that epithelial cell derived Fizz1 is sufficient to increase the bone-marrow derived dendritic cells in the lungs, but it is not sufficient to cause lung fibrosis or alter chemical or particle-induced fibrosis.
Highlights
Resistin-like molecule alpha or found in inflammatory zone protein (Fizz1) is increased in pulmonary epithelial cells and in limited amounts by other lung cells during various lung injuries and fibrosis
Clara cell secretory protein (CCSP)/Fizz1 mice on Dox demonstrated about 14.1 fold increases in the signal intensity at 9.5 kDa corresponding to a mature Fizz1 protein in lung homogenates over lung homogenates from mice not treated with Dox (Figure 1B)
The current study demonstrates that constitutive overexpression of Fizz1 in lung epithelial cells increases the percentage of bone marrow derived hematopoietic cells in the lung
Summary
Resistin-like molecule alpha or found in inflammatory zone protein (Fizz1) is increased in pulmonary epithelial cells and in limited amounts by other lung cells during various lung injuries and fibrosis. Lung remodeling in the distal airspace and parenchyma is characterized by excessive extracellular matrix deposition and accumulation of apoptosis-resistant and collagen producing myofibroblasts. There are no effective therapeutic treatments available for pulmonary fibrosis highlighting the importance of identifying targetable cells, fibrogenic pathways and molecules to design therapeutic approaches and to use as biomarkers of preponderance and induction of Fizz occurs through IL13/IL4-driven STAT 6 activation. In vitro studies demonstrate that Fizz activates type I collagen expression in fibroblasts via a notch1dependent pathway [10]. Fizz transforms fibroblasts to collagen producing myofibroblasts and induces anti-apoptotic responses in myofibroblasts contributing to excess myofibroblast accumulation and production of extracellular matrix proteins in the lung [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
