| Background:Over-expression of WISP1has been described in various organsfibrosis and tissues remodeling. Moreover, it has been recently found thatpolymorphism of WISP1gene is related with the change of lung function inasthmatic subjects. Therefore, we hypothesized that WISP1is closelylinked to occurrence and development of asthmatic airway remodeling.Objective:Aim of this study was to examine the roles of WISP1in an asthmaticmodel of airway remodeling and assess the specific effects of WISP1onhuman lung fibroblast (HFL-1) in vitro.Methods:Asthma models with airway remodeling in rats were developed bychallenged with ovalbumin. The levels of WISP1expression in animalmodels were assessed by Real-Time PCR and immunohistochemistry. Toexamine the specific effects of WISP1on airway remodeling, WISP1wasdepleted by neutralizing α-WISP1antibodies in vivo. Moreover, human lung fibroblast (HFL-1) was challenged with WISP1in the presence andabsence of SH-5in vitro. HFL-1proliferation and collagen deposition wereassessed by MTT and Western Blot, the levels of p-Akt and p-GSK-3βwere quantificationally detected by Western Blot.Results:1. Our studies showed that OVA exposure increased the levels ofWISP1expression in the animal model. WISP1depletion could partlyinhibit OVA-induced airway remodeling.2. WISP1-treated HFL-1cells presented abnormal proliferation andover-expression of Col1a1and Fn1in vitro.3. WISP1-induced collagen release from HFL-1cells could beattenuated by the pretreatment with an Akt inhibitor.4. The levels of p-Akt and p-GSK-3β in WISP1-treated HFL-1cellswere also significantly elevated, but the process was also significantlysuppressed by the pretreatment with an Akt inhibitor.Conclusion:1. WISP1may initiate and perpetuate the pathological remodeling ofasthma by induced fibroblast proliferation and ECM deposition.2. The pro-remodeling effect of WISP1is likely due tophosphorylation and inactivation of pulmonary GSK-3β under activation ofAkt signaling pathway. |
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