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Insect Science 2024年第4期31卷 1090-1106页

作者： Yi Wei Xiao-Lin Zhou Peng Chen Tai-Hang Liu Cheng Lu Min-Hui Pan State Key Laboratory of Silkworm Genome Biology Southwest UniversityChongqingChina Key Laboratory for Sericulture Functional Genomics and Biotechnology of Agricultural Ministry Southwest UniversityChongqingChina Wenzhou Institute University of Chinese Academy of SciencesWenzhouZhejiang ProvinceChina

The ovary generally undergoes tissue remodeling during larval to pupal transition,which includes membrane degeneration and ovariole *** the same time,the hormones produced by insects significantly change during ***,the regulatory mechanism for ovarian development and hormones is not fully understood in ***,we found that matrix metalloproteinase 2(MMP2)was highly expressed in the ovarian capsules and ovarioles,and the development was abnormal after knocking out MMP2 in Bombyx *** process of abnormal degradation of collagen I due to MMP2 deletion,which resulted in abnormal development of ovarioles and eggs,was analyzed in *** proteomics of ovaries in the MMP2-knock out and wild type strains showed a critically significant difference in the expression of a protein,insulin-like peptide(ILP).Additional analysis revealed significant alteration of ILP during ovarian development,and abnormal expression of ILP significantly affected ovarian development in vivo and MMP2 expression in vitro and in *** results showed that MMP2 regulation of ovarian tissue remodeling is closely related to ILP *** study provides new insights into the regulatory mechanism of MMP2 and ovarian development in ***.

关键词： Bombyx mori collagen I insulin-like peptide matrix metalloproteinase ovarian development

matrix metalloproteinase 2 contributes to adult eclosion and immune response in the small hive beetle,Aethina tumida

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Insect Science 2024年第3期31卷 733-747页

作者： Lixian Wu Yajing Xu Liangbin Li Dainan Cao Fang Liu Hongxia Zhao Guangdong Key Laboratssory of Animal Conservation and Resource Utilization Guangdong Public Laboratory of Wild Animal Conservation and UtilizationInstitute of ZoologyGuangdong Academy of SciencesGuangzhouChina

During the pupal-adult eclosion process of holometabolous insects,the old cuticle is shed and replaced by a completely different new cuticle that requires tanning and expansion,along with extensive extracellular matrix(ECM)*** vertebrates,matrix metalloproteinases(MMPs),a class of zinc-dependent endopeptidases,play key roles in regulating the ECM that surrounds ***,little is known about these extracellular proteinases available in *** small hive beetle(SHB),Aethina tumida,is a widespread invasive parasite of honey *** this study,6 MMP homologs were identified in the SHB *** interference experiments showed that all 6 AtMmps are not required for the larval-pupal transition,only AtMmp2 was essential for pupal-adult eclosion in *** of AtMmp2 resulted in eclosion defects and wing expansion failure,as well as mortality within 3 d of adult *** analysis revealed that knockdown of AtMmp2 significantly increased expression of the Toll and Imd pathways,chitin metabolism,and cross-linking(such as the pro-phenoloxidase activating cascade pathway and the tyrosine-mediated cuticle sclerotization and pigmentation pathway).These data revealed evolutionarily conserved functions of Mmp2 in controlling adult eclosion and wing expansion,also provided a preliminary exploration of the novel function of regulating Toll and Imd pathways,as well as new insights into how MMPs regulate insect development and defense barriers.

关键词： Aethina tumida adult eclosion immune response matrix metalloproteinase RNAinterference

matrix metalloproteinase-9 in the Etiopathogenesis of Placenta Accreta Spectrum:A Literature Review

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Maternal-Fetal Medicine 2024年第2期6卷 97-101页

作者： Putri Mirani Peby Maulina Lestari Krisna Murti Iche Andriyani Liberty Hana Andrina Cindy Kesty Bella Stevanny Division of Maternal-Fetal Medicine Department of Obstetrics and GynecologyDr.Mohammad Hoesin General Hospital/Faculty of Medicine Sriwijaya UniversityPalembangSouth SumateraIndonesia Division of Hematolymphoid and Endocrinology Department of Pathological AnatomyDr.Mohammad Hoesin General Hospital/Faculty of Medicine Sriwijaya UniversityPalembangIndonesia Department of Public Health and Community Medicine Faculty of MedicineSriwijaya UniversityPalembangIndonesia Department of Obstetrics and Gynecology Dr.Mohammad Hoesin General Hospital/Faculty of Medicine Sriwijaya UniversityPalembangSouth SumateraIndonesia.

The recent increase in placenta accreta spectrum has been correlated with a rise in the rate of cesarean sections.A recent study provides evidence that hampered wound healing results in cesarean scar defects that lead to a failure in the normal process of decidualization and deeper adherence of *** metalloproteinase(MMP)is crucial in every step of wound healing as it alters the wound matrix,facilitating cell migration,as well as tissue ***-9 expression is higher in placental and decidual tissue in cases of placenta *** on these findings,assessment of MMP-9 expression can shed new light on the etiopathology of placenta accreta spectrum disorder and can be a potential diagnostic marker.

关键词： Biomarker Etiopathogenesis matrix metalloproteinase MMP-9 Placenta accreta spectrum disorder

matrix metalloproteinase-9 contributes to parenchymal hemorrhage and necrosis in the remnant liver after extended hepatectomy in mice

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World Journal of Gastroenterology 2012年第19期18卷 2320-2333页

作者： Norifumi Ohashi Tomohide Hori Florence Chen Sura Jermanus Christopher B Eckman Akimasa Nakao Shinji Uemoto Justin H Nguyen Gastroenterological Surgery Nagoya University Graduate School of MedicineNagoyaAichi 466-8550Japan Divisions of Hepato-Pancreato-Biliary Transplant and Pediatric SurgeryDepartment of SurgeryKyoto University Graduate School of MedicineKyoto 606-8507Japan Department of Neuroscience Mayo ClinicJacksonvilleFL 32224United States Division of Transplant Surgery Department of TransplantationMayo ClinicJacksonvilleFL 32224United States

AIM： To investigate the effect of matrix metallopro- teinase-9 （MMP-9） on the remnant liver after massivehepatectomy in the mouse.METHODS： Age-matched, C57BL/6 wild-type （WT）, MMP-9（-/-）, and tissue inhibitors of metalloprotein- ases （TIMP）-1（-/-） mice were used. The mice received 80%-partial hepatectomy （PH）. Samples were obtained at 6 h after 80%-PH, and we used histology, immuno- histochemical staining, western blotting analysis and zymography to investigate the effect of PH on MMP-9. The role of MMP-9 after PH was investigated using a monoclonal antibody and MMP inhibitor.RESULTS： We examined the remnant liver 6 h after 80%-PH and found that MMP-9 deficiency attenuated the formation of hemorrhage and necrosis. There were significantly fewer and smaller hemorrhagic and ne- crotic lesions in MMP-9（-/-） remnant livers compared with WT and TIMP-1（-/-） livers （P 〈 0.01）, with no dif- ference between WT and TIMP-1（-/-） mice. Serum ala- nine aminotransaminase levels were significantly lower in MMP-9（-/-） mice compared with those in TIMP-I（-/-） mice （WT： 476± 83 IU/L, MMP-9（-/-）： 392 ± 30 IU/L, TIMP-I（-/-）： 673 ± 73 IU/L, P 〈 0.01）. Western blot- ting and gelatin zymography demonstrated a lack of MMP-9 expression and activity in MMP-9（-/-） mice, which was in contrast to WT and TIMP-1（-/-） mice. No change in MMP-2 expression was observed in any of the study groups. Similar to MMP-9（-/-） mice, when WT mice were treated with MMP-9 monoclonal antibody or the synthetic inhibitor GM6001, hemorrhagic and necrotic lesions were significantly smaller and fewer than in control mice （P 〈 0.05）. These results suggest that MMP-9 plays an important role in the development of parenchymal hemorrhage and necrosis in the small remnant liver.CONCLUSION： Successful MMP-9 inhibition attenuates the formation of hemorrhage and necrosis and mightbe a potential therapy to ameliorate liver injury after massive hepatectomy.

关键词： matrix metalloproteinase Liver remnant Hepatectomy Liver failure Necrosis

matrix metalloproteinase AND THEIR INHIBITORS: MOLECULAR ASPECTS OF THEIR ROLES IN THE TUMOR METASTASIS

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Chinese Journal of Cancer Research 2000年第4期12卷 239-243页

作者：李克勤李春海 Department of Tumor Molecular Biology Beijing Basic Medical Institute and North Taiping Road Hospital Beijing China

The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, whose physiological functions include tissue remo-delling and embryogenesis. The importance of this group of proteins in the processes of tumor invasion and metastasis is now widely acknowledged, and has led to the search for MMP inhibitors for use as anticancer treatments in a clinical setting. The review aims to introduce current research relating to MMPs as well as their native and synthetic inhibitor, with particular emphasis on the molecular aspects of their roles in tumor metastasis.

关键词： matrix metalloproteinase Tissue inhibitor of matrix metalloproteinase Tumor Gene regulation

Ethanol Extract of Lycopodium serratum Thunb. Attenuates Lipopolysaccharide-Induced C6 Glioma Cells Migration via matrix metalloproteinase-9 Expression

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Chinese Journal of Integrative Medicine 2018年第11期24卷 860-866页

作者： Ju-Yeon Park Hyuck Kim Dong-Woo Lim Jai-Eun Kim Won-Hwan Park Sun-Dong Park Institute of Korean Medicine College of Korean Medicine Dongguk University Department of Diagnostics College of Korean Medicine Dongguk University Department of Pathology College of Korean Medicine Dongguk University Department of Prescription College of Korean Medicine Dongguk University

Objectives： To elucidate how ethanol extract of L. serratum（ELS） could exert anti-migratory effects on glioma with the suppression of nuclear factor kappa B（NF-κB） downstream pathway. Methods： Cell viability of ELS on C6 glioma was detected by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） assay. Nitric oxide（NO） assay and 2＇,7＇-dichlorofluorescin diacetate（DCFH-DA） assay were applied to measure NO production and reactive oxygen species（ROS） generation on lipopolysaccharide（LPS）-induced C6 glioma cells. NF-κB, mitogen-activated protein kinase（MAPK）, inducible nictric oxide synthase（i NOS） and cyclooxygenase-2（COX-2） protein were determined by Western blot. Wound healing assay was used to investigate the inhibitory effect of ELS on fetal bovine serum（FBS）-induced migration and matrix metalloproteinase（MMP）-9 and-2 activity was examined by zymography. Results： ELS suppressed LPS-induced phosphorylation of extracellular signal-regulated kinase（ERK）, c-Jun N-terminal kinase（JNK）, and p38 through inhibiting the expression of chemokine CCL2（or monocyte chemoattractant protein-1, MCP-1）. In addition, ELS inhibited the expression of i NOS, COX-2, and the production of NO by LPS in C6 glioma cells. ELS also significantly decreased serum-induced migration of C6 glioma cells in scratch wound healing in a dose-dependent manner（P〈0.01）. The activity of MMP-9 and-2 were also significantly attenuated by ELS with LPS treatment（P〈0.01）. Conclusion： Our results suggest that downregulation of MMP-9 gene expression might be involved in the anti-migration effect of ELS against LPS-induced C6 glioma cells.

关键词： Lycopodium serratum Thunb lipopolysaccharide matrix metalloproteinase migration C6 glioma cell

Occurrence of cGMP/nitric oxide-sensitive store-operated calcium entry in fibroblasts and its effect on matrix metalloproteinase secretion

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World Journal of Gastroenterology 2006年第34期12卷 5483-5489页

作者： Yong Huang Min-Qiang Lu Hua Li Chi Xu Shu-Hong Yi Gui-Hua Chen Liver Transplantation Centre the Third Affiliated Hospital Sun Yat-Sen University Guangzhou 510630 Guangdong Province China

AIM： To examine the existence of Nitric oxide/ cGMP sensitive store-operated Ca^2＋ entry in mouse fibroblast NIH/3T3 cells and its influence on matrix metalloproteinase （MMP） production and adhesion ability of fibroblasts. METHODS： NIH/3T3 cells were cultured. Confocal laser scanning microscopy was used to examine the existence of thapsigargin-induced store-operated Ca^2＋ entry in fibroblasts. Gelatin zymography and semiquantitative reverse transcriptase-polymerase chain reaction （RTPCR） were employed to detect the involvement of [Ca^2＋]i and NO/cGMP in MMP secretion. The involvement of NO/ cGMP-sensitive Ca^2＋ entry in adhesion was determined using matrigel-coated culture plates. RESULTS： 8-bromo-cGMP inhibited the thapsigargin-induced Ca^2＋ entry in 3T3 cells. The cGMP-induced inhibition was abolished by an inhibitor of protein kinase G, KT5823 （1μmol/L）. A similar effect on the Ca^2＋ entry was observed in 3T3 cells in response to a NO donor, （±）-S-nitroso-N-acetylpenicillamine （SNAP）. The inhibitory effect of SNAP on the thapsigargin-induced Ca^2＋ entry was also observed, indicating NO/cGMP-regulated Ca^2＋ entry in 3T3 cells. Results of gelatin zymography assay showed that addition of extracellular Ca^2＋ concentration induced MMP release and activation in a dose-dependent manner. RT-PCR also showed that cGMP and SNAP reduced the production of MMP mRNA in 3T3 cells. Experiments investigating adhesion potentials demonstrated that cGMP and SNAP could upgrade 3T3 cell attachment rate to the matrigel-coated culture plates.CONCLUSION： NO/cGMP sensitive store-operated Ca^2＋ entry occurs in fibroblasts, and attenuates their adhesion potentials through its influence on MMP secretion.

关键词： cGMP Nitric oxide Protein kinase G Storeoperated Ca^2+ entry matrix metalloproteinase Fibroblast

Variants of genes encoding collagens and matrix metalloproteinase system increased the risk of aortic dissection

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Science China(Life Sciences) 2017年第1期60卷 57-65页

作者： Zongzhe Li Chengming Zhou Lun Tan Peng Chen Yanyan Cao Chenze Li Xianqing Li Jiangtao Yan Hesong Zeng Dao-Wu Wang Dao-Wen Wang Division of Cardiology Departments of Internal Medicine and Genetic Diagnosis CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Cardiology the First Affiliated HospitalNanjing Medical University

Aortic dissection （AD） is a devastating, heterogeneous condition of aorta. The homeostasis between collagens and matrix metalloproteases （MMPs）/tissue inhibitors of MMPs （TIMPs） system in the extracellular matrix plays an important role for structure and functions of aorta. However, our knowledge on association between variants of genes in this system and pathogenesis of AD is very limited. We analyzed all yet known coding human genes of collagens （45 genes）, MMPs/TIMPs （27 genes） in 702 sporadic AD patients and in 163 matched healthy controls, by using massively targeted next-generation and Sanger sequencing. To define the pathogenesis of potential disease-causing candidate genes, we performed transcriptome sequencing and pedigree co-segregation analysis in some genes and generated Col5a2 knockout rats. We identified 257 pathogenic or likely pathogenic variants which involved 88.89% （64/72） genes in collagens-MMPs/TIMPs system and accounted for 31.05% （218/702） sporadic AD patients. In them, 84.86% patients （185/218） carried one variant, 12.84% two variants and 2.30% more than two variants. Importantly, we identified 52 novel probablY pathogenic loss-of-function （LOF） variants （20 nonsense, 16 frameshift, 14 splice sites, one stop-loss, one initiation codon） in 11.06% （50/452） AD patients, which were absent in 163 controls （P=2.5-10-5）. Transcriptome sequencing revealed that identified variants induced dyshomeostasis in expression of collagens-TIMPs/MMPs systems. The Col5a2-/- rats manifested growth retardation and aortic dysplasia. Our study provides a first comprehensive map of genetic alterations in collagens-MMPs/TIMPs system in sporadic AD patients and suggests that variants of these genes contribute largely to AD pathogenesis.

关键词： aortic dissection collagen matrix metalloproteinase next-generation sequencing genetic diagnosis

Membrane-type Ⅰ matrix metalloproteinase(MT1-MMP),lipid metabolism,and therapeutic implications

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Journal of Molecular Cell Biology 2021年第7期13卷 513-526页

作者： Xiao-Dan Xia Adekunle Alabi Maggie Wang Hong-Mei Gu Rui Zhe Yang Gui-Qing Wang Da-Wei Zhang Department of Orthopedics The Sixth Affiliated Hospital(Qingyuan People’s Hospital)Guangzhou Medical UniversityQingyuan 511500China Department of Pediatrics and Group on the Molecular and Cell Biology of Lipids Faculty of Medicine and DentistryUniversity of AlbertaEdmontonAB T6R 2G3Canada

Lipids exert many essential physiological functions,such as serving as a structural component of biological membranes,storing energy,and regulating cell signal *** of lipid metabolism can lead to dyslipidemia related to various human diseases,such as obesity,diabetes,and cardiovascular ***,lipid metabolism is strictly regulated through multiple mechanisms at different levels,including the extracellular ***-type I matrix metalloproteinase(MT1-MMP),a zinc-dependent endopeptidase,proteolytically cleaves extracellular matrix components,and non-matrix proteins,thereby regulating many physiological and pathophysiological *** evidence supports the vital role of MT1-MMP in lipid *** example,MT1-MMP mediates ectodomain shedding of low-density lipoprotein receptor and increases plasma low-density lipoprotein cholesterol levels and the development of *** also increases the vulnerability of atherosclerotic plaque by promoting collagen ***,it can cleave the extracellular matrix of adipocytes,affecting adipogenesis and the development of ***,the activity of MT1-MMP is strictly regulated by multiple mechanisms,such as autocatalytic cleavage,endocytosis and exocytosis,and post-translational ***,we summarize the latest advances in MT1-MMP,mainly focusing on its role in lipid metabolism,the molecular mechanisms regulating the function and expression of MT1-MMP,and their pharmacotherapeutic implications.

关键词： matrix metalloproteinase low-density lipoprotein receptor extracellular matrix atherosclerosis cardiovascular disease obesity

Circumvent PEGylation dilemma by implementing matrix metalloproteinase-responsive chemistry for promoted tumor gene therapy

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Chinese Chemical Letters 2020年第12期31卷 3143-3148页

作者： Jingyun Wang Hao Wang Hongyan Cui Peng Sun Xi Yang Qixian Chen State Key Laboratory of Fine Chemicals Dalian University of TechnologyDalian 116024China School of Bioengineering Dalian University of TechnologyDalian 116024China Department of Neurosurgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China

Surface modification by poly(ethylene glycol)(PEGylation)has been acknowledged as a powerful strategy in minimizing non-specific reactions for biomedical *** applied into manufacture of drug/gene delivery systems,PEGylation has demonstrated to significantly improve their biocompatibility and stealthiness in physiological ***,reluctant cell membrane affinities thus cellular uptake efficiencies owing to PEGylation brought up further issues that are imperative to be *** to this PEGylation dilemma,we attempted to introduce peptide(GPLGVRG)linkage between block copolymer of PEG-poly{N’-[N-(2-aminoethyl)-2-aminoethyl]aspartamide}PAsp(DET),wherein the cationic PAsp(DET)could self-assemble with pDNA into nanoscaled complex *** was the peptide linkage whose amino acids sequence could be specifically recognized and degraded by matrix metalloproteinases(MMPs)(overexpressed in extracellular milieu of tumors).Therefore,our subsequent studies validated facile detachment of PEGylation from the aforementioned polyplex micelles upon treatment of MMPs,which elicited improved cytomembrane affinities and cellular uptake *** addition,promoted escape from endosome entrapment was also confirmed through direct endosome membrane destabilization by PAsp(DET),which was further elucidated to be attributable to dePEGylation as well as elevated charged density of PAsp(DET)in acidic *** benefits from dePEGylation eventually contributed to promoted gene expression at the affected cells and potent tumor growth suppression based on anti-angiogenic ***,our developed strategy has provided a facile approach in overcoming the dilemma of PEGylation,which could be informative in design of drug/gene delivery systems.

关键词： PEGylation Tumor Polyplex micelle Gene delivery system matrix metalloproteinase