功能性消化不良(FD)的胃肠动力障碍与Cajal间质细胞(ICC)网络损伤密切相关。文章系统阐述干细胞因子(SCF)/c-kit信号通路在FD发病中的核心作用,提出柴桂和胃方通过三重机制修复ICC网络:1) 柴胡皂苷激活c-kit受体促ICC增殖;2) 桂枝成分...功能性消化不良(FD)的胃肠动力障碍与Cajal间质细胞(ICC)网络损伤密切相关。文章系统阐述干细胞因子(SCF)/c-kit信号通路在FD发病中的核心作用,提出柴桂和胃方通过三重机制修复ICC网络:1) 柴胡皂苷激活c-kit受体促ICC增殖;2) 桂枝成分抑制肿瘤坏死因子-α (TNF-α)改善炎症微环境;3) 白芍苷调节5-羟色胺(5-HT)信号恢复脑肠轴平衡。基于“肝郁脾虚-ICC功能障碍”病机对应理论,构建中药复方多靶点修复胃肠起搏网络的新假说,为中西医结合治疗提供理论依据。Gastrointestinal dyskinesia in functional dyspepsia (FD) is closely related to the damage of Cajal interstitial cell (ICC) network. In this paper, the central role of the stem cell factor (SCF)/c-kit signaling pathway in the pathogenesis of FD was systematically elucidated, and it was proposed that the Chai Gui Hewei Decoction repaired the ICC network through a three-fold mechanism: 1) Bupleurum saponin activated the c-kit receptor to promote the proliferation of ICC;2) Cinnamomum cassiae ingredient inhibited the tumor necrosis factor-α (TNF-α) to improve the inflammation microenvironment;3) Paeonia lactiflora glucoside regulates 5-hydroxytryptamine (5-HT) signaling to restore the balance of brain-gut axis. Based on the theory of “liver depression and spleen deficiency-ICC dysfunction”, a new hypothesis of multi-target repair of gastrointestinal pacing network by traditional Chinese herbal medicine compound was constructed, which provides a theoretical basis for the combination of Chinese and Western medicine.展开更多
胃肠动力障碍性疾病(disorders of gastrointestinal motility,DGIM)是指因胃肠动力失常引起的以消化道症状为主要临床表现的疾病。DGIM的发病率有逐年升高的趋势,降低人们生活质量的同时,还增加了社会的医疗支出。DGIM的发病机制尚未...胃肠动力障碍性疾病(disorders of gastrointestinal motility,DGIM)是指因胃肠动力失常引起的以消化道症状为主要临床表现的疾病。DGIM的发病率有逐年升高的趋势,降低人们生活质量的同时,还增加了社会的医疗支出。DGIM的发病机制尚未完全阐明,多项研究表明其发生发展与胃肠道动力异常关系密切。胃肠动力与胃肠道Cajal间质细胞(ICC)密切相关。ICC是胃肠道产生慢波运动的特殊细胞,ICC数量和形态的保持又与SCF/c-kit信号通路密切相关。近年来的研究表明,SCF/c-kit信号通路的异常改变可导致DGIM的发生。目前,DGIM的西医治疗主要为促动力及抑酸等对症治疗,在一定程度上能够缓解DGIM的症状,但常伴有不良反应,使药物的应用范围受限,而大量研究证实,中药、中药单体或成分、复方、中医外治法均可通过调节SCF/c-kit信号通路,有效改善胃肠动力的同时,不良反应较小。虽然中医药通过调控SCF/c-kit信号通路干预DGIM具有西医难以取代的独特优势,但目前中医药调控SCF/c-kit信号通路治疗DGIM系统综述仍较少。文章就SCF/c-kit信号通路与DGIM之间的相关性、中医药调控SCF/c-kit信号通路干预DGIM的作用机制进行系统性总结,旨在为临床治疗DGIM及新药研发提供新思考。展开更多
The SKP1 gene is an important component of the SCF(SKP1-Cullin1-F-box)complex and serves as a bridge connecting the F-box and Cullin1genes(F-box-SKP1-Cullin1).The pattern of S-RNase being ubiquitously labelled by the ...The SKP1 gene is an important component of the SCF(SKP1-Cullin1-F-box)complex and serves as a bridge connecting the F-box and Cullin1genes(F-box-SKP1-Cullin1).The pattern of S-RNase being ubiquitously labelled by the SCF complex and degraded by the 26S protease accounts for the bulk of the available self-incompatibility studies.In this study,15 ClSKP1s from the‘Xiangshui'lemon genome and ubiquitome exist in the same SKP1 conserved domain(CD)as SKP1s in other species.The q PCR results showed that SKP1-6 and SKP1-14 have tissue expression patterns specific for expression in pollen.In addition,SKP1-6 and SKP1-14 in the stigma,style and ovary were significantly upregulated after self-pollination compared to those after cross-pollination.A subcellular location showed that SKP1-6 and SKP1-14 were located in the nucleus.In addition,yeast two-hybrid(Y2H)assays,bimolecular fluorescence complementation(BiFC)and luciferase complementation imaging(LCI)assays showed that SKP1-6 interacted with F-box1,F-box33,F-box34,F-box17,F-box19,Cullin1-2 and 26S proteasome subunit 4 homolog A(26S PS4HA).SKP1-14 interacted with F-box17,F-box19,F-box35,Cullin1-2 and 26S PS4HA.The interaction of Cullin1-2 and the F-box with SKP1 as a bridge was verified by a yeast three-hybrid experiment.The ability of S3-RNase to inhibit pollen and pollen tube growth and development was assessed using in vitro pollen co-culture experiments with recombinant S3-RNase proteins.Overall,this study provides important experimental evidence and theoretical basis for understanding the mechanism of self-incompatibility in plants by revealing the key role of the SCF complex in‘Xiangshui'lemon,which is bridged by ClSKP1-6,in self-incompatibility.The results of this study are of great significance for the future indepth exploration of the molecular mechanism of the SCF complex and its wide application in the self-incompatibility of plants.展开更多
文摘功能性消化不良(FD)的胃肠动力障碍与Cajal间质细胞(ICC)网络损伤密切相关。文章系统阐述干细胞因子(SCF)/c-kit信号通路在FD发病中的核心作用,提出柴桂和胃方通过三重机制修复ICC网络:1) 柴胡皂苷激活c-kit受体促ICC增殖;2) 桂枝成分抑制肿瘤坏死因子-α (TNF-α)改善炎症微环境;3) 白芍苷调节5-羟色胺(5-HT)信号恢复脑肠轴平衡。基于“肝郁脾虚-ICC功能障碍”病机对应理论,构建中药复方多靶点修复胃肠起搏网络的新假说,为中西医结合治疗提供理论依据。Gastrointestinal dyskinesia in functional dyspepsia (FD) is closely related to the damage of Cajal interstitial cell (ICC) network. In this paper, the central role of the stem cell factor (SCF)/c-kit signaling pathway in the pathogenesis of FD was systematically elucidated, and it was proposed that the Chai Gui Hewei Decoction repaired the ICC network through a three-fold mechanism: 1) Bupleurum saponin activated the c-kit receptor to promote the proliferation of ICC;2) Cinnamomum cassiae ingredient inhibited the tumor necrosis factor-α (TNF-α) to improve the inflammation microenvironment;3) Paeonia lactiflora glucoside regulates 5-hydroxytryptamine (5-HT) signaling to restore the balance of brain-gut axis. Based on the theory of “liver depression and spleen deficiency-ICC dysfunction”, a new hypothesis of multi-target repair of gastrointestinal pacing network by traditional Chinese herbal medicine compound was constructed, which provides a theoretical basis for the combination of Chinese and Western medicine.
文摘胃肠动力障碍性疾病(disorders of gastrointestinal motility,DGIM)是指因胃肠动力失常引起的以消化道症状为主要临床表现的疾病。DGIM的发病率有逐年升高的趋势,降低人们生活质量的同时,还增加了社会的医疗支出。DGIM的发病机制尚未完全阐明,多项研究表明其发生发展与胃肠道动力异常关系密切。胃肠动力与胃肠道Cajal间质细胞(ICC)密切相关。ICC是胃肠道产生慢波运动的特殊细胞,ICC数量和形态的保持又与SCF/c-kit信号通路密切相关。近年来的研究表明,SCF/c-kit信号通路的异常改变可导致DGIM的发生。目前,DGIM的西医治疗主要为促动力及抑酸等对症治疗,在一定程度上能够缓解DGIM的症状,但常伴有不良反应,使药物的应用范围受限,而大量研究证实,中药、中药单体或成分、复方、中医外治法均可通过调节SCF/c-kit信号通路,有效改善胃肠动力的同时,不良反应较小。虽然中医药通过调控SCF/c-kit信号通路干预DGIM具有西医难以取代的独特优势,但目前中医药调控SCF/c-kit信号通路治疗DGIM系统综述仍较少。文章就SCF/c-kit信号通路与DGIM之间的相关性、中医药调控SCF/c-kit信号通路干预DGIM的作用机制进行系统性总结,旨在为临床治疗DGIM及新药研发提供新思考。
基金supported by grants from the National Natural Science Foundation of China(Grant No.31960585)Science and Technology Major Project of Guangxi(Grant No.Guike AA22068092)+1 种基金Guangxi Science and Technology Vanguard Special Action Project(Grant No.202204)State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources(Grant Nos.SKLCUSA-a201906,SKLCU-SA-c201901)。
文摘The SKP1 gene is an important component of the SCF(SKP1-Cullin1-F-box)complex and serves as a bridge connecting the F-box and Cullin1genes(F-box-SKP1-Cullin1).The pattern of S-RNase being ubiquitously labelled by the SCF complex and degraded by the 26S protease accounts for the bulk of the available self-incompatibility studies.In this study,15 ClSKP1s from the‘Xiangshui'lemon genome and ubiquitome exist in the same SKP1 conserved domain(CD)as SKP1s in other species.The q PCR results showed that SKP1-6 and SKP1-14 have tissue expression patterns specific for expression in pollen.In addition,SKP1-6 and SKP1-14 in the stigma,style and ovary were significantly upregulated after self-pollination compared to those after cross-pollination.A subcellular location showed that SKP1-6 and SKP1-14 were located in the nucleus.In addition,yeast two-hybrid(Y2H)assays,bimolecular fluorescence complementation(BiFC)and luciferase complementation imaging(LCI)assays showed that SKP1-6 interacted with F-box1,F-box33,F-box34,F-box17,F-box19,Cullin1-2 and 26S proteasome subunit 4 homolog A(26S PS4HA).SKP1-14 interacted with F-box17,F-box19,F-box35,Cullin1-2 and 26S PS4HA.The interaction of Cullin1-2 and the F-box with SKP1 as a bridge was verified by a yeast three-hybrid experiment.The ability of S3-RNase to inhibit pollen and pollen tube growth and development was assessed using in vitro pollen co-culture experiments with recombinant S3-RNase proteins.Overall,this study provides important experimental evidence and theoretical basis for understanding the mechanism of self-incompatibility in plants by revealing the key role of the SCF complex in‘Xiangshui'lemon,which is bridged by ClSKP1-6,in self-incompatibility.The results of this study are of great significance for the future indepth exploration of the molecular mechanism of the SCF complex and its wide application in the self-incompatibility of plants.
