Stanniocalcin-1,A Candidate Epithelium-derived Relaxing Factor In Asthma

Background:Asthma is a common chronic disease characterized by airway hyper-responsiveness?AHR?,inflammation and airway remodeling.AHR results from abnormal airway smooth muscle?ASM?contraction regulated by Ca²⁺homeostasis.An epithelium-derived relaxing factor?EpDRF?is proposed to exist in healthy epithelium to regulate ASM contraction.Stanniocalcin-1?STC1?,a secreted protein,has been reported to modulate Ca²⁺homeostasis.We preliminarily explored the expression levels of STC1 in asthma patients and the function of STC1 on AHR,to investigate whether STC1 was a novel EpDRF.Objective:To investigate the expression levels of STC1 in asthma patients and the function of STC1 on AHR.Methods:Serum levels of STC1 in asthma patients and BALF levels in asthma mice were measured by ELISA.Using OVA-induced asthma mouse,the effect of STC1 on AHR was measured by whole-body barometric plethysmography and the effect of STC1 on inflammation was studied by Hematoxylin and Eosin Staining and inflammation scoring.The STC1 expression site was studied by immunohisto-chemistry.And the mRNA and protein levels of STC1 in human bronchial epithelial?16HBE?cells were measured by real-time polymerase chain reaction?RT-PCR?and Western blot.The function of STC1 on Ca²⁺influx was researched by calcium imaging and on ASM contraction was discussed by cell contraction assay.Results:Serum levels of STC1 were decreased in asthma patients compared with healthy volunteers and positively correlated with the degree of asthma control and with lung function.STC1 was mainly expressed in bronchial epithelium and intratracheal administration of recombinant human STC1?rhSTC1?to a mouse model of asthma reduced AHR and inflammation.In vitro,the secretion of STC1 from human bronchial epithelial?16HBE?cells was suppressed by IL-13,where rhSTC1given blocked Ca²⁺influx,further inhibited ASM cells contractility by suppressing Ca²⁺-dependent myosin light chain?MLC?phosphorylation.Conclusion:Our data indicates that STC1 deficiency in asthma may be associated with ASM contraction and AHR which suggests that STC1 may be a candidate EpDRF.