title: A role for WNT1-inducible signaling protein-1 in airway remodeling in a rat asthma model.
abstract: Over-expression of WISP1 has been described in multi-organ fibrosis and tissue remodeling. Moreover, it has recently been found that polymorphism of WISP1 gene is related with the change of lung function in asthmatic subjects. Therefore, we hypothesized that WISP1 might be closely linked to occurrence and development of asthmatic airway remodeling. Aim of this study was to examine the roles of WISP1 in an asthmatic model with airway remodeling and assess the specific effects of WISP1 on human lung fibroblast in vitro. Animal models were developed by challenged with ovalbumin. The levels of WISP1 expression in animal models were assessed by real-time PCR and immunohistochemistry. To examine the specific effects of WISP1 on airway remodeling, WISP1 was depleted by neutralizing α-WISP1 antibodies in vivo. Moreover, human lung fibroblast (HFL-1) was challenged with WISP1 in the presence and absence of SH-5 in vitro. Our study showed that OVA exposure increased the levels of WISP1 expression in a rat asthma model. WISP1 depletion could partially inhibit OVA-induced airway remodeling. In vitro, WISP1-treated HFL-1 cells presented abnormal proliferation and over-expression of Col1a1 and Fn1. However, WISP1-induced collagen release from HFL-1 cells could be attenuated by pretreatment with an Akt inhibitor. Moreover, the levels of p-Akt and p-GSK-3β in WISP1-treated HFL-1 cells were also significantly elevated. In summary, WISP1 might initiate and perpetuate the pathological remodeling of asthma by inducing fibroblast proliferation and ECM deposition. The specific effects of WISP1 were likely due to activation of pulmonary Akt/GSK-3β signaling.
authors.affiliation: Department of Respiratory Medicine, Chongqing Medical University, Chongqing, China.
authors.forename: Mingjin
authors.initials: M
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Yuanyin
authors.initials: Y
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Tian
authors.forename: Xuemei
authors.initials: X
authors.lastname: Ran
authors.forename: Youfan
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D055511:CCN Intercellular Signaling Proteins / Q000191:economics / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007295:Inositol Phosphates / Q000494:pharmacology; D008168:Lung / Q000473:pathology; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins / Q000191:economics / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C435044:1-((1-O-octadecyl-2-O-methylglycero)phospho)-3-deoxy-myo-inositol; D019138:Antibodies, Blocking; D055511:CCN Intercellular Signaling Proteins; C492066:CCN4 protein, rat; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D007295:Inositol Phosphates; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D010047:Ovalbumin
keywords: Airway remodeling; Akt signaling pathway; Asthma; GSK-3β; Lung fibroblast; WISP1