Weiwei Decoction alleviates gastric intestinal metaplasia through the olfactomedin 4/nucleotide-binding oligomerization domain 1/caudaltype homeobox gene 2 signaling pathway  

作　　者：Di-Shu Zhou Wei-Jian Zhang Shu-Ya Song Xin-Xin Hong Wei-Qin Yang Juan-Juan Li Jian-Qu Xu Jian-Yuan Kang Tian-Tian Cai Yi-Fei Xu Shao-Ju Guo Hua-Feng Pan Hai-Wen Li 

机构地区：[1]Shenzhen Traditional Chinese Medicine Hospital,The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine,Shenzhen 518033,Guangdong Province,China [2]Science and Technology Innovation Center,Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong Province,China [3]Department of Chinese Medicine,The Eight Affiliated Hospital,Sun Yat-Sen University,Shenzhen 518033,Guangdong Province,China

出　　处：《World Journal of Gastrointestinal Oncology》2024年第7期3211-3229,共19页世界胃肠肿瘤学杂志(英文)

基　　金：Supported by National Natural Science Foundation of China,No.82104747 and No.82305133;Basic and Applied Basic Research Foundation of Guangdong Province,China,No.2020A1515110947;General Project of Shenzhen Science and Technology Innovation Commission,No.JCYJ20230807094659030,No.JCYJ20230807094805012,No.JCYJ20210324111602007,and No.JCYJ20220531091815034;the Scientific Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine,No.20221349.

摘　　要：BACKGROUND Gastric intestinal metaplasia(IM)is a precancerous lesion that is associated with an elevated risk of gastric carcinogenesis.Weiwei Decoction(WWD)is a promising traditional Chinese herbal formula widely employed in clinical for treating IM.Previous studies suggested the potential involvement of the olfactomedin 4(OLFM4)/nucleotide-binding oligomerization domain 1(NOD1)/caudal-type homeobox gene 2(CDX2)signaling pathway in IM regulation.AIM To verify the regulation of the OLFM4/NOD1/CDX2 pathway in IM,specifically investigating WWD’s effectiveness on IM through this pathway.METHODS Immunohistochemistry for OLFM4,NOD1,and CDX2 was conducted on tissue microarray.GES-1 cells treated with chenodeoxycholic acid were utilized as IM cell models.OLFM4 short hairpin RNA(shRNA),NOD1 shRNA,and OLFM4 pcDNA were transfected to clarify the pathway regulatory relationships.Protein interactions were validated by coimmunoprecipitation.To explore WWD’s pharmacological actions,IM rat models were induced using N-methyl-N’-nitro-N-nitrosoguanidine followed by WWD gavage.Gastric cells were treated with WWD-medicated serum.Cytokines and chemokines content were assessed by enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction.RESULTS The OLFM4/NOD1/CDX2 axis was a characteristic of IM.OLFM4 exhibited direct binding and subsequent downregulation of NOD1,thereby sustaining the activation of CDX2 and promoting the progression of IM.WWD improved gastric mucosal histological lesions while suppressing intestinal markers KLF transcription factor 4,villin 1,and MUCIN 2 expression in IM rats.Regarding pharmacological actions,WWD suppressed OLFM4 and restored NOD1 expression,consequently reducing CDX2 at the mRNA and protein levels in IM rats.Parallel regulatory mechanisms were observed at the protein level in IM cells treated with WWD-medicated serum.Furthermore,WWD-medicated serum treatment strengthened OLFM4 and NOD1 interaction.In case of antiinflammatory,WWD restrained interleukin(

关 键 词：Gastric intestinal metaplasia Weiwei Decoction Olfactomedin 4 Nucleotide-binding oligomerization domain 1 Caudal-type homeobox gene 2 Gastric cancer 

分 类 号：R73[医药卫生—肿瘤]