Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is incre...Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is increasing yearly.Hypertension is a major risk factor for cardiovascular disease.Wnt signaling comprises a series of highly conservative cascading events controlling fundamental biological processes.Wnt signaling pathways include the canonical Wnt pathway(or Wnt/β-catenin pathway),the non canonical planar cell-polarity pathway,and the non-canonical calcium-dependent pathways.Abnormal Wnt signaling promotes cell proliferation and differentiation,cardiac malformations,various malignancies,so drugs targeting Wnt signaling play a great therapeutic potential.Wnt/β-catenin pathway is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis and stroke by regulating cell proliferation,migration,apoptosis,blood-brain barrier permeability,inflammation,oxidative stress,and immune response.Based on the latest research progress,this review summarizes the role of Wnt/β-catenin signaling in cardiovascular diseases,in order to provide new ideas for the prevention and treatment of cardiovascular diseases.展开更多
OBJECTIVE To investigate the pharmacological effect of ursolic acid(UA)on colitis-associated colorectal cancer(CAC)and its underlying mechanism based on the Wnt signaling pathway.METHODS The CAC model in mice was esta...OBJECTIVE To investigate the pharmacological effect of ursolic acid(UA)on colitis-associated colorectal cancer(CAC)and its underlying mechanism based on the Wnt signaling pathway.METHODS The CAC model in mice was established by azoxymethane(AOM)combined and dextran sulfate sodium salt(DSS),accompanied by treatment with various dosages of UA and concomitant appraisal of body weight,stool and physical state of the mice.After the sacrifice of the mice,the tumor and length of the colorectum were measured,followed by retrieval of the liver,spleen,thymus and tumor tissue for downstream assays.The levels of inflammatory factors interleukin-6(IL-6),IL^(-1)βand C-reactive protein(CRP)in the tumor and serum were examined by enzyme-linked immunosorbent assay(ELISA).The pathological changes of colorectal tissues were observed by HE staining.The levels in tumors of Wnt/β-catenin signaling pathway-related proteins Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1 and apoptosis-related protein Bcl-2 were assayed by immunohistochemistry(IHC).The mRNA expressions of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,Bax,caspase-9 and caspase-3 in tumors were detected by real-time quantitative RT-PCR(RT-qPCR).The protein levels of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,phospho-β-catenin,phospho-GSK-3β,Bcl-2 and Bax in tumors were probed by analyzed by Western blotting(WB).Also,RNA-seq was employed to assess the gut microbiota in the mice.RESULTS UA significantly ameliorated the symptoms of AOM/DSS-induced mouse CAC,evidenced by improved physical state,body weight,survival rate,colorectal length,the mass of liver,thymus,spleen,and decreased CAC load and colorectal mass.UA attenuated the levels of IL-6,IL^(-1)βand CRP in the mouse serum and colorectal tumor in a dose-dependent manner.HE staining showed that UA lessened carcinogenesis in the colorectum,with lower infiltration of lymphocytes,versus the control.IHC indicated that UA mitigated the expression of Wnt4,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,and promoted the GSK-3βexpression,compared with the control.Furthermore,UA diminished the mRNA expressions of Wnt4,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,and heightened the mRNA levels of GSK-3β,caspase-3,capase-9 and Bax in CAC.The results of mRNA expressions were verified by WB analysis,which revealed that UA impeded the protein expression of Wnt4,β-catenin,c-Myc,cyclin D1,Bcl-2,TCF4,LEF1,and elevated the protein levels of GSK-3βand Bax,phospho-β-catenin in mouse CAC.In addition,UA substantially ameliorated the gut microbiota to store the metabolic function in the mice with CAC.CONCLUSION Ursolic acid may protect against CAC,potentially by downregulation of Wnt/β-catenin signaling pathway activity and restoration of gut microbiota.展开更多
文摘Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is increasing yearly.Hypertension is a major risk factor for cardiovascular disease.Wnt signaling comprises a series of highly conservative cascading events controlling fundamental biological processes.Wnt signaling pathways include the canonical Wnt pathway(or Wnt/β-catenin pathway),the non canonical planar cell-polarity pathway,and the non-canonical calcium-dependent pathways.Abnormal Wnt signaling promotes cell proliferation and differentiation,cardiac malformations,various malignancies,so drugs targeting Wnt signaling play a great therapeutic potential.Wnt/β-catenin pathway is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis and stroke by regulating cell proliferation,migration,apoptosis,blood-brain barrier permeability,inflammation,oxidative stress,and immune response.Based on the latest research progress,this review summarizes the role of Wnt/β-catenin signaling in cardiovascular diseases,in order to provide new ideas for the prevention and treatment of cardiovascular diseases.
基金National Natural Science Foundation of China(81573813,81173598)Sichuan Provincial Admin⁃istration of Traditional Chinese Medicine of China(2021MS447)+1 种基金Excellent Talent Program of Chengdu University of Tra⁃ditional Chinese Medicine of China(YXRC2019002,ZRYY1917)Open Research Fund of the State Key Laboratory of Southwestern Chinese Medicine Resources of China(2020XSGG006)。
文摘OBJECTIVE To investigate the pharmacological effect of ursolic acid(UA)on colitis-associated colorectal cancer(CAC)and its underlying mechanism based on the Wnt signaling pathway.METHODS The CAC model in mice was established by azoxymethane(AOM)combined and dextran sulfate sodium salt(DSS),accompanied by treatment with various dosages of UA and concomitant appraisal of body weight,stool and physical state of the mice.After the sacrifice of the mice,the tumor and length of the colorectum were measured,followed by retrieval of the liver,spleen,thymus and tumor tissue for downstream assays.The levels of inflammatory factors interleukin-6(IL-6),IL^(-1)βand C-reactive protein(CRP)in the tumor and serum were examined by enzyme-linked immunosorbent assay(ELISA).The pathological changes of colorectal tissues were observed by HE staining.The levels in tumors of Wnt/β-catenin signaling pathway-related proteins Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1 and apoptosis-related protein Bcl-2 were assayed by immunohistochemistry(IHC).The mRNA expressions of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,Bax,caspase-9 and caspase-3 in tumors were detected by real-time quantitative RT-PCR(RT-qPCR).The protein levels of Wnt4,GSK-3β,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,phospho-β-catenin,phospho-GSK-3β,Bcl-2 and Bax in tumors were probed by analyzed by Western blotting(WB).Also,RNA-seq was employed to assess the gut microbiota in the mice.RESULTS UA significantly ameliorated the symptoms of AOM/DSS-induced mouse CAC,evidenced by improved physical state,body weight,survival rate,colorectal length,the mass of liver,thymus,spleen,and decreased CAC load and colorectal mass.UA attenuated the levels of IL-6,IL^(-1)βand CRP in the mouse serum and colorectal tumor in a dose-dependent manner.HE staining showed that UA lessened carcinogenesis in the colorectum,with lower infiltration of lymphocytes,versus the control.IHC indicated that UA mitigated the expression of Wnt4,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,and promoted the GSK-3βexpression,compared with the control.Furthermore,UA diminished the mRNA expressions of Wnt4,β-catenin,TCF4,LEF1,c-Myc,cyclin D1,Bcl-2,and heightened the mRNA levels of GSK-3β,caspase-3,capase-9 and Bax in CAC.The results of mRNA expressions were verified by WB analysis,which revealed that UA impeded the protein expression of Wnt4,β-catenin,c-Myc,cyclin D1,Bcl-2,TCF4,LEF1,and elevated the protein levels of GSK-3βand Bax,phospho-β-catenin in mouse CAC.In addition,UA substantially ameliorated the gut microbiota to store the metabolic function in the mice with CAC.CONCLUSION Ursolic acid may protect against CAC,potentially by downregulation of Wnt/β-catenin signaling pathway activity and restoration of gut microbiota.
