PMID- 38409837 OWN - NLM STAT- MEDLINE DCOM- 20240228 LR - 20240228 IS - 1944-7930 (Electronic) IS - 1539-6509 (Linking) VI - 36 IP - 181 DP - 2024 Feb TI - SFRP5 Partially Inhibits the Proliferation and Migration of Airway Smooth Muscle Cells in Children with Asthma by Regulating the Wnt/beta-Catenin Signaling Pathway. PG - 323-331 LID - 10.24976/Discov.Med.202436181.30 [doi] AB - 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 mug/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 beta-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 beta-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)/beta-catenin pathway. FAU - Yuan, Yuyun AU - Yuan Y AD - Department of Pediatrics, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, 201999 Shanghai, China. FAU - Zhu, Honghua AU - Zhu H AD - Department of Medical Imaging, Shanghai Seventh People's Hospital, 200137 Shanghai, China. FAU - Huang, Sihong AU - Huang S AD - Department of Pediatrics, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, 201999 Shanghai, China. FAU - Zhang, Yantao AU - Zhang Y AD - Department of Pediatrics, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, 201999 Shanghai, China. FAU - Shen, Yiyun AU - Shen Y AD - Department of Pediatrics, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, 201999 Shanghai, China. LA - eng PT - Journal Article PL - United States TA - Discov Med JT - Discovery medicine JID - 101250006 RN - 1B56C968OA (Becaplermin) RN - 0 (beta Catenin) RN - 0 (SFRP5 protein, human) RN - 0 (Adaptor Proteins, Signal Transducing) SB - IM MH - Animals MH - Child MH - Mice MH - Humans MH - Becaplermin/metabolism/pharmacology MH - *beta Catenin/metabolism/pharmacology MH - Wnt Signaling Pathway/genetics MH - *Asthma/genetics/metabolism/pathology MH - Cell Proliferation/genetics MH - Lung/metabolism MH - Cell Movement MH - Myocytes, Smooth Muscle/metabolism/pathology MH - Cells, Cultured MH - Adaptor Proteins, Signal Transducing/metabolism OTO - NOTNLM OT - HASMCs OT - SFRP5 OT - Wnt/beta-catenin OT - children with asthma OT - migration OT - proliferation EDAT- 2024/02/27 06:45 MHDA- 2024/02/28 06:45 CRDT- 2024/02/27 02:29 PHST- 2024/02/28 06:45 [medline] PHST- 2024/02/27 06:45 [pubmed] PHST- 2024/02/27 02:29 [entrez] AID - 1708325300281-1780721949 [pii] AID - 10.24976/Discov.Med.202436181.30 [doi] PST - ppublish SO - Discov Med. 2024 Feb;36(181):323-331. doi: 10.24976/Discov.Med.202436181.30.