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Published on: October 16, 2016
SFRP5 Partially Inhibits the Proliferation and Migration of Airway Smooth Muscle Cells in Children with Asthma by
Yuyun Yuan1, Honghua Zhu2, Sihong Huang1
1Department of Pediatrics, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, 201999 Shanghai, China.
Insights
Secreted frizzled-related protein 5 (SFRP5) levels are lower in children with asthma. Increasing SFRP5 in airway cells helps reduce asthma-related inflammation and cell growth.
Area of Science:
- Respiratory Medicine
- Immunology
- Cell Biology
Background:
- Childhood asthma is a chronic respiratory inflammatory disease.
- Secreted frizzled-related protein 5 (SFRP5) is potentially linked to respiratory inflammation.
- Investigating SFRP5's role in human airway smooth muscle cells (HASMCs) may offer new asthma treatment strategies.
Purpose of the Study:
- To investigate the effect of SFRP5 on human airway smooth muscle cells (HASMCs).
- To explore SFRP5's potential role in childhood asthma pathogenesis.
- To provide novel therapeutic insights for asthma treatment.
Main Methods:
- Serum SFRP5 levels were measured in children with asthma and healthy controls using ELISA and RT-qPCR.
- SFRP5 overexpression or control vectors were transfected into HASMCs.
- HASMCs were treated with platelet-derived growth factor-BB (PDGF-BB) to induce asthma-like conditions.
- Cell proliferation, migration, and protein expression (Wnt/β-catenin pathway) were analyzed.
Main Results:
- Serum SFRP5 levels were significantly decreased in children with asthma compared to healthy controls.
- PDGF-BB treatment reduced SFRP5 expression and increased HASMC proliferation, migration, and Wnt/β-catenin pathway activation.
- SFRP5 overexpression partially inhibited PDGF-BB-induced HASMC proliferation and migration.
Conclusions:
- Serum SFRP5 expression is reduced in childhood asthma.
- SFRP5 overexpression mitigates PDGF-BB-induced HASMC proliferation and migration.
- SFRP5 may exert its effects by regulating the Wnt/β-catenin pathway in asthma.
Background:
Childhood asthma is a chronic inflammatory disease of the respiratory tract characterized by bronchial inflammation, airway hyperresponsiveness, airflow disorder, and obstruction. Secreted frizzled-related protein 5 (SFRP5) may be associated with respiratory inflammatory diseases. This study investigated the effect of SFRP5 on human airway smooth muscle cells (HASMCs) to provide new ideas for treating asthma.
Methods:
A total of 30 children with asthma and 30 children who had a physical examination at the same time were selected and divided into asthma and healthy groups. Serum SFRP5 levels were determined by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (RT-qPCR). Lipofectamine 2000™ regent was used to transfect the SFRP5 overexpression plasmid (pc-SFRP5) or corresponding negative control (pc-NC) into HASMCs. HASMCs were treated with 10 μg/L platelet-derived growth factor-BB (PDGF-BB), which is an inducer to mimic the asthma-like condition at the cellular level of childhood asthma. HASMCs were divided into control, PDGF-BB (PDGF-BB treatment), PDGF-BB+pc-NC (pc-NC transfection and PDGF-BB treatment), and PDGF-BB+pc-SFRP5 (pc-SFRP5 transfection and PDGF-BB treatment) groups. Cell proliferation was measured by 5-ethynyl-2'-deoxyuridine (EdU) and cell counting kit-8 (CCK-8) assay. Cell migration was detected by Transwell assay. The protein expression was detected by western blot.
Results:
Serum SFRP5 expression in the asthmatic group was decreased versus the healthy group (p < 0.0001). Induction of PDGF-BB decreased SFRP5 expression in HASMCs (p < 0.01). SFRP5 expression in the pc-SFRP5 group was increased (p < 0.01). The proliferation and migration of HASMCs increased after PDGF-BB treatment (p < 0.001, p < 0.0001), indicating that the asthma model was successfully inducted in vitro. Moreover, the expression of β-catenin, cellular-myelocytomatosis viral oncogene (c-Myc), and cyclinD1 proteins in HASMCs increased after PDGF-BB treatment (p < 0.0001). SFRP5 overexpression partly inhibited PDGF-BB-induced proliferation, migration, and expressions of β-catenin, c-Myc, and cyclinD proteins in HASMCs (p < 0.01, p < 0.001, p < 0.0001).
Conclusions:
Serum SFRP5 expression decreases in children with asthma. SFRP5 overexpression partially inhibits PDGF-BB-induced HASMC proliferation and migration by regulating the wingless-type mouse mammary tumor virus (MMTV) integration site family (Wnt)/β-catenin pathway.
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