MSCs attenuate airway remodeling in HDM-induced asthma by inhibiting the Timp1-Wnt2b axisOA
MSCs have demonstrated their unique therapeutic potential in early clinical trials for a variety of respiratory diseases in recent years,but their use in the treatment of asthma has rarely been reported.In this study,a chronic murine asthma model that is more similar to clinical asthma is constructed via sustained HDM induction for 70 days,followed by treatment via tail vein injection of MSCs after modeling.The mechanism by which MSCs alleviate airway remodeling is investigated via RNA-seq.The airways on the day following treatment are used to screen for transcriptomic changes resulting from the MSC treatment under study,filtering for differentially expressed genes(DEGs),identifying their enrichment pathways,and finally confirming the DEGs gained via western blot analysis.After HDM treatment,airway remodeling is reversed,asthma and the HIF-1 signaling pathway are inhibited,and the expression levels of Timp1 and Wnt2b in the fibrosis pathway are also significantly decreased.STRiNG analysis reveals a reciprocal interaction in their expression,which is also confirmed by western blot analysis.To verify whether MSCs alleviate airway remodeling by inhibiting Timp1,we construct MSCs overexpressing Timp1 and evaluate their effects in vitro and in vivo.The ability of MSCs to alleviate airway remodeling is reversed after Timp1 is overexpressed.These findings demonstrate that MSCs alleviate asthma-induced airway remodeling by inhibiting the Timp1-Wnt2b axis.
Kai Yu;Xinyu Feng;Rong Zhang;Jian Fan;Jiaying Yuan;Yan Shang;Jiayi Zhao
Department of General Practice,Changhai Hospital,Naval Military Medical University,Shanghai 200433,ChinaDepartment of General Practice,411 Hospital,Shanghai University,Shanghai 200081,ChinaDepartment of Respiratory and Critical Care Medicine,Changhai Hospital,Naval Military Medical University,Shanghai 200433,ChinaDepartment of General Practice,Changhai Hospital,Naval Military Medical University,Shanghai 200433,ChinaDepartment of Respiratory and Critical Care Medicine,Changhai Hospital,Naval Military Medical University,Shanghai 200433,ChinaDepartment of General Practice,Changhai Hospital,Naval Military Medical University,Shanghai 200433,ChinaDepartment of General Practice,411 Hospital,Shanghai University,Shanghai 200081,China Department of General Practice,Shanghai 411 Hospital,China RongTong Medical Healthcare Group Co.Ltd.,Shanghai 200081,China
医药卫生
airway remodelingasthmaMSCTimp1Wnt2b
《Acta Biochimica et Biophysica Sinica》 2026 (2)
P.396-405,10
The grants from the National Natural Science Foundation of China(No.82170033)the Natural Science Foundation of Shanghai(No.21ZR1479200)the Shanghai"Community Medicine and Health Management Research Project Research"special fund(No.2023SQ01)the Medical Research Project Plan of Shanghai Hongkou District Municipal Health Committee(Nos.HW2302-43 and HW2302-44)the 2022 Shanghai Rehabilitation Medical Association“Rehabilitation Science and Technology Innovation Program"(No.2022KJCx007).The authors declare that they have no conflict of interest.
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