The Relationship Between FSTL1 And Airway Remodeling In Asthmatics

BackgroundBronchial asthma is a heterogeneous disease and now considered to be a chronic airway inflammatory disease involved with inflammatory cells,airway structural cells and a variety of cells components.The three main pathological features of asthma include airway chronic airway inflammation,airway smooth dysfunction and airway remodeling.Airway remodeling encompasses variety of structural changes that occurs in airways,including epithelial metaplasia,goblet cells proliferation and mucus secretion,subepithelial fibrosis,smooth muscle mass increasing,angiogenesis and so on.These pathological changes can cause airway hyperresponsiveness,airway mucus hypersecretion,airway wall thickening and airway stenosis,and consequently cause irreversible clinical outcome.Follistatin-like protein 1(FSTL1)is an extracellular glycoprotein which is composed of 308 aminoacids and can be found in human plasma and several tissues.The function of FSTL1 is not clear but recent studies suggest that FSTL1 has a certain relationship with the development of respiratory system and the development of respiratory diseases like asthma.ObjectivesTo analyze the difference of the plasma FSTL1 level between asthmatics and the normal.To evaluate the correlation between plasma FSTL1 level and a series of clinical parameters in asthma.To identify the correlation between FSTL1in plasma and BALF and airway remodeling.To observe the relationship between FSTL1 in BALF and markers of airway remodeling.To explore the role and potential mechanism of FSTL1 in asthma and the development of airway remodeling.To discuss the clinical significance in diagnosis of asthma and monitoring airway remodeling by detecting level of FSTL1.MethodsThis study included 32 subjects with asthma from Qilu hospital of Shandong University and 25 subjects who visited our hospital for a routine medical checkup.All subjects enrolled had blood routine examination and pulmonary function testing.We examined the FSTL1 level in the plasma from all the subjects.Besides,15 of the 32 asthmatics underwent fibrotic bronchoscopy,bronchoalveolar lavage and endobronchial biopsy.ELISA(enzyme linked immunosorbent assay)was used to detect the level of FSTL1 in plasma and BALF.H&E(hematoxylin and eosin)staining was performed to observe the pathological changes in the epithelial tissues.PSAM(periodic acid-silver metheramin)staining was used to detect the thickness of basement membrane and Sirius red staining was used for observation of the fibrosis around airway.Immunohistochemical staining were performed to assess the correlation between FSTL1 and markers of airway remodeling,a-SMA and collagen I.During our observing period,we collected the blood samples and other clinical auxiliary examinations of the reexamined subjects.Spearman rank analysis was performed to detect the correlation between plasma FSTL1 and other parameters.ResultsPlasma FSTL1 levels were significantly higher in asthmatics(130.762±46.029 ng/ml)than in controls(95.408±33.938ng/ml)(p=0.009).There was a positive relationship between FSTL1 levels in plasma and BALF(rs=0.550,p=0.034).The expression of FSTL1 in asthmatic airway epithelium is significantly higher than in normal airway epithelium(p<0.001).Plasma FSTL1 levels were associated with fibrosis around airways(rs=0.529.p=0.043)and the expression of α-SMA(rs=0.554,p=0.032).And FSTL1 levels in BALF were associated with the expression of collagen I(rs=0.536.p=0.040).a-SMA(rs=0.561,p=0.029),fibrosis around airways(rs=0.779,p=0.001)and the thickness of airway reticular basement membrane(rs=0.660,p=0.007).After the treatment of asthma for one month,plasma FSTL1 levels declined significantly(p<0.001).ConclusionsHigher FSTL1 levels in asthmatics were associated to increased smooth muscle mass and thickened airway basement membrane.FSTL1 may contribute to airway remodeling in asthma patients.