The therapeutic potential of Annexin A1,an important member of the Annexin superfamily,has become evident in results of experiments with multiple human systems and animal models.The anti-inflammatory and pro-resolving...The therapeutic potential of Annexin A1,an important member of the Annexin superfamily,has become evident in results of experiments with multiple human systems and animal models.The anti-inflammatory and pro-resolving effects of Annexin A1 are characteristic of pathologies involving the nervous system.In this review,we initially describe the expression sites of Annexin A1,then outline the mechanisms by which Annexin A1 maintains the neurological homeostasis through either formyl peptide receptor 2 or other molecular approaches;and,finally,we discuss the neuroregenerative potential qualities of Annexin A1.The eye and the nervous system are anatomically and functionally connected,but the association between visual system pathogenesis,especially in the retina,and Annexin A1 alterations has not been well summarized.Therefore,we explain the beneficial effects of Annexin A1 for ocular diseases,especially for retinal diseases and glaucoma on the basis of published findings,and we explore present and future delivery strategies for Annexin A1 to the retina.展开更多
2024年8月23日,北京大学心血管研究所、北京大学血管稳态与重构全国重点实验室郑乐民教授团队在Signal Transduction and Targeted Therapy杂志上在线发表了题为“Annexin A1 binds PDZ and LIM domain 7 to inhibit adipogene-sis and ...2024年8月23日,北京大学心血管研究所、北京大学血管稳态与重构全国重点实验室郑乐民教授团队在Signal Transduction and Targeted Therapy杂志上在线发表了题为“Annexin A1 binds PDZ and LIM domain 7 to inhibit adipogene-sis and prevent obesity”的研究论文。该研究报道了膜联蛋白A1(annexin A1,ANXA1)通过与MYC结合蛋白2(MYCBP2)竞争性结合PDZ和LIM结构域7(PDLIM7)进而影响SMAD4泛素化蛋白酶体降解和脂肪生成进程的新机制,揭示了该通路在抗肥胖功能的潜在治疗策略,并提出了采用ANXA1模拟肽进行抗肥胖治疗的可能性。展开更多
●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in spe...●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in specific pathogen free environment as the control group(n=10),and the rats fed in dry environment as the dryness group(n=10).After 24d,lacrimal glands were collected from the rats.The tissues morphology was observed by hematoxylineosin(HE)staining.Tandem mass tags(TMT)quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups,then bioinformatics analysis was performed.Further,the immunohistochemical(IHC)method was used to verify the target proteins.●RESULTS:In dryness group,the lacrimal glands lobule atrophied,the glandular cavities enlarged,the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed.The proteomics exhibited that a total of 195 up-regulated and 236 downregulated differential expressed proteins screened from the lacrimal glands of rats.It was indicated that the biological processes(BP)of differential expressed proteins mainly included cell processes and single BP.The cellular compositions of differential expressed proteins mainly located in cells,organelles.The molecular functions of differential expressed proteins mainly included binding,catalytic activity.Moreover,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that the differential expressed proteins mainly involved lysosome,complement and coagulation cascade,and ribosome pathway.The IHC result verified that the up-regulated expression proteins of Protein S100A9(S100A9),Annexin A1(Anxa1),and Clusterin(Clu)in lacrimal glands of rats in dryness group were higher than control group.●CONCLUSION:The up-regulated expression proteins of S100A9,Anxa1,and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment.This study provides clues of dry environments causing eye-related diseases for further studies.展开更多
BACKGROUND Hepatic fibrosis is a common pathological process of chronic liver diseases with various causes,which can progress to cirrhosis.AIM To evaluate the effect and mechanism of action annexin(Anx)A1 in liver fib...BACKGROUND Hepatic fibrosis is a common pathological process of chronic liver diseases with various causes,which can progress to cirrhosis.AIM To evaluate the effect and mechanism of action annexin(Anx)A1 in liver fibrosis and how this could be targeted therapeutically.METHODS CCl4(20%)and active N-terminal peptide of AnxA1(Ac2-26)and N-formylpeptide receptor antagonist N-Boc-Phe-Leu-Phe-Leu-Phe(Boc2)were injected intraperitoneally to induce liver fibrosis in eight wild-type mice/Anxa1 knockout mice,and to detect expression of inflammatory factors,collagen deposition,and the role of the Wnt/β-catenin pathway in hepatic fibrosis.RESULTS Compared with the control group,AnxA1,transforming growth factor(TGF)-β1,interleukin(IL)-1βand IL-6 expression in the liver of mice with hepatic fibrosis induced by CCl4 was significantly increased,which promoted collagen deposition and expression ofα-smooth muscle actin(α-SMA),collagen type I and connective tissue growth factor(CTGF),and increased progressively with time.CCl4 induced an increase in TGF-β1,IL-1βand IL-6 in liver tissue of AnxA1 knockout mice,and the degree of liver inflammation and fibrosis and expression ofα-SMA,collagen I and CTGF were significantly increased compared with in wild-type mice.After treatment with Ac2-26,expression of liver inflammatory factors,degree of collagen deposition and expression of a-SMA,collagen I and CTGF were decreased compared with before treatment.Boc2 inhibited the anti-inflammatory and antifibrotic effects of Ac2-26.AnxA1 downregulated expression of the Wnt/β-catenin pathway in CCl4-induced hepatic fibrosis.In vitro,lipopolysaccharide(LPS)induced hepatocyte and hepatic stellate cell(HSC)expression of AnxA1.Ac2-26 inhibited LPS-induced RAW264.7 cell activation and HSC proliferation,decreased expression ofα-SMA,collagen I and CTGF in HSCs,and inhibited expression of the Wnt/β-catenin pathway after HSC activation.These therapeutic effects were inhibited by Boc2.CONCLUSION AnxA1 inhibited liver fibrosis in mice,and its mechanism may be related to inhibition of HSC Wnt/β-catenin pathway activation by targeting formylpeptide receptors to regulate macrophage function.展开更多
基金supported by the National Natural Science Foundation of China,Nos.31800868(to YZ),32271037(to XL)and 82271090(to HZ).
文摘The therapeutic potential of Annexin A1,an important member of the Annexin superfamily,has become evident in results of experiments with multiple human systems and animal models.The anti-inflammatory and pro-resolving effects of Annexin A1 are characteristic of pathologies involving the nervous system.In this review,we initially describe the expression sites of Annexin A1,then outline the mechanisms by which Annexin A1 maintains the neurological homeostasis through either formyl peptide receptor 2 or other molecular approaches;and,finally,we discuss the neuroregenerative potential qualities of Annexin A1.The eye and the nervous system are anatomically and functionally connected,but the association between visual system pathogenesis,especially in the retina,and Annexin A1 alterations has not been well summarized.Therefore,we explain the beneficial effects of Annexin A1 for ocular diseases,especially for retinal diseases and glaucoma on the basis of published findings,and we explore present and future delivery strategies for Annexin A1 to the retina.
文摘2024年8月23日,北京大学心血管研究所、北京大学血管稳态与重构全国重点实验室郑乐民教授团队在Signal Transduction and Targeted Therapy杂志上在线发表了题为“Annexin A1 binds PDZ and LIM domain 7 to inhibit adipogene-sis and prevent obesity”的研究论文。该研究报道了膜联蛋白A1(annexin A1,ANXA1)通过与MYC结合蛋白2(MYCBP2)竞争性结合PDZ和LIM结构域7(PDLIM7)进而影响SMAD4泛素化蛋白酶体降解和脂肪生成进程的新机制,揭示了该通路在抗肥胖功能的潜在治疗策略,并提出了采用ANXA1模拟肽进行抗肥胖治疗的可能性。
基金Supported by Regional Science Foundation Project of the National Natural Science Foundation of China(No.82060827,No.82260891)The Key Discipline of Universities in the“14th Five-Year Plan”Autonomous Region-Traditional Chinese Medicine at Xinjiang Medical University.
文摘●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in specific pathogen free environment as the control group(n=10),and the rats fed in dry environment as the dryness group(n=10).After 24d,lacrimal glands were collected from the rats.The tissues morphology was observed by hematoxylineosin(HE)staining.Tandem mass tags(TMT)quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups,then bioinformatics analysis was performed.Further,the immunohistochemical(IHC)method was used to verify the target proteins.●RESULTS:In dryness group,the lacrimal glands lobule atrophied,the glandular cavities enlarged,the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed.The proteomics exhibited that a total of 195 up-regulated and 236 downregulated differential expressed proteins screened from the lacrimal glands of rats.It was indicated that the biological processes(BP)of differential expressed proteins mainly included cell processes and single BP.The cellular compositions of differential expressed proteins mainly located in cells,organelles.The molecular functions of differential expressed proteins mainly included binding,catalytic activity.Moreover,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that the differential expressed proteins mainly involved lysosome,complement and coagulation cascade,and ribosome pathway.The IHC result verified that the up-regulated expression proteins of Protein S100A9(S100A9),Annexin A1(Anxa1),and Clusterin(Clu)in lacrimal glands of rats in dryness group were higher than control group.●CONCLUSION:The up-regulated expression proteins of S100A9,Anxa1,and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment.This study provides clues of dry environments causing eye-related diseases for further studies.
基金a Grant-in-Aid for Scientific Research from National Natural Science Foundation of China,No. 81860120 and 81860104Guangxi Natural Science Foundation,No. 2017GXNSFBA198134, 2017GXNSFAA198299 and 2015GXNSFCA139024
文摘BACKGROUND Hepatic fibrosis is a common pathological process of chronic liver diseases with various causes,which can progress to cirrhosis.AIM To evaluate the effect and mechanism of action annexin(Anx)A1 in liver fibrosis and how this could be targeted therapeutically.METHODS CCl4(20%)and active N-terminal peptide of AnxA1(Ac2-26)and N-formylpeptide receptor antagonist N-Boc-Phe-Leu-Phe-Leu-Phe(Boc2)were injected intraperitoneally to induce liver fibrosis in eight wild-type mice/Anxa1 knockout mice,and to detect expression of inflammatory factors,collagen deposition,and the role of the Wnt/β-catenin pathway in hepatic fibrosis.RESULTS Compared with the control group,AnxA1,transforming growth factor(TGF)-β1,interleukin(IL)-1βand IL-6 expression in the liver of mice with hepatic fibrosis induced by CCl4 was significantly increased,which promoted collagen deposition and expression ofα-smooth muscle actin(α-SMA),collagen type I and connective tissue growth factor(CTGF),and increased progressively with time.CCl4 induced an increase in TGF-β1,IL-1βand IL-6 in liver tissue of AnxA1 knockout mice,and the degree of liver inflammation and fibrosis and expression ofα-SMA,collagen I and CTGF were significantly increased compared with in wild-type mice.After treatment with Ac2-26,expression of liver inflammatory factors,degree of collagen deposition and expression of a-SMA,collagen I and CTGF were decreased compared with before treatment.Boc2 inhibited the anti-inflammatory and antifibrotic effects of Ac2-26.AnxA1 downregulated expression of the Wnt/β-catenin pathway in CCl4-induced hepatic fibrosis.In vitro,lipopolysaccharide(LPS)induced hepatocyte and hepatic stellate cell(HSC)expression of AnxA1.Ac2-26 inhibited LPS-induced RAW264.7 cell activation and HSC proliferation,decreased expression ofα-SMA,collagen I and CTGF in HSCs,and inhibited expression of the Wnt/β-catenin pathway after HSC activation.These therapeutic effects were inhibited by Boc2.CONCLUSION AnxA1 inhibited liver fibrosis in mice,and its mechanism may be related to inhibition of HSC Wnt/β-catenin pathway activation by targeting formylpeptide receptors to regulate macrophage function.
