DKK1 Positively Correlates with Lung Function in COPD Patients and Reduces Airway Inflammation

Abstract

Luqi Dai,1,2,* Dan Xu,1,* Chun Wan,1,2 Lian Liu,1 Fuqiang Wen1,2 1Division of Pulmonary Diseases, State Key Laboratory of Biotherapy, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fuqiang Wen; Lian LiuDepartment of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, and Division of Pulmonary Diseases, State Key Laboratory of Biotherapy, Guoxuexiang 37 Road, Chengdu, Sichuan, 610041, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]; [email protected]: WNT/β-catenin signal pathway is a potential hope for lung tissue repair. We investigated the levels of Dickkopf‐1 (DKK1), an endogenous inhibitor of WNT/β-catenin signal pathway, in chronic obstructive pulmonary disease (COPD) patients and airway inflammation.Patients and Methods: Collected the demographic and clinical characteristics of 36 healthy controls, 25 stable COPD patients and 10 acute exacerbation of COPD (AECOPD) patients, then performed pulmonary function and detected serum DKK1 levels. After over-expression of DKK1, detect the levels of DDK1, lipoprotein-related protein 6 (LRP6) and inflammatory factors in bronchial epithelial cells stimulated with cigarette smoke extract (CSE).Results: Serum DKK1 were reduced in stable COPD patients compared to healthy controls (3866.72 ± 775.33 pg/mL vs 5317.61 ± 1317.20 pg/mL, p 0.05). DKK1 was positively correlated with FEV1 (r = 0.570, p< 0.0001), FEV1/FVC (rho = 0.590, p< 0.0001), FEV1/Pre (r = 0.517, p< 0.0001). Multiple linear regression analysis also suggested that FEV1 levels were higher with increasing DKK1. In vitro, elevated IL-6, IL-8, TNF-α and decreased DKK1, LRP6 were found in Beas-2B cells after CSE treatments, and increased LRP6 and decreased inflammatory factors were found after overexpression of DKK1. Andrographolide restored the CSE-induced decrease in DKK1 and increase in IL-6 and IL-8.Conclusion: DKK1 levels were decreased in COPD patients and positively correlated with lung function, overexpression of DKK1 and andrographolide attenuated airway cell inflammation, both suggesting a potential role in pathophysiology and providing a disease-specific biomarker pattern.Keywords: LRP6, lung function, biomarker, andrographolide

Keywords

• lrp6
• lung function
• biomarker
• andrographolide