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Matrix metalloproteases and their tissue inhibitors in non-alcoholic liver fibrosis of human immunodeficiency virus-infected patients

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World Journal of Virology 2017年第2期6卷 36-45页

作者： Julio Collazos Eulalia Valle-Garay Tomás Suárez-Zarracina Angel-Hugo Montes José A Cartón Víctor Asensi Infectious Diseases Hospital de Galdácano Biochemistry and Molecular Biology Hospital Universitario Central de AsturiasOviedo University School of Medicine Infectious Diseases Hospital Universitario Central de AsturiasOviedo University School of Medicine

AIM To investigate the relationships among diverse metalloproteases(MMPs) and their tissue inhibitors(TIMPs) and non-alcoholic liver fibrosis in human immunodeficiency virus(HIV)-infected patients.METHODS Single nucleotide polymorphisms(SNPs) in MMPs, TNF-α and CCR5 genes, and serum levels of MMPs and TIMPs were determined in HIV-infected individuals with/out hepatitis C virus(HCV) coinfection. A total of 158 patients were included, 57 of whom were HCVcoinfected. All patients drank < 50 g ethanol/day. Diverse SNPs(MMP-1-1607 1G/2G, MMP-8-799C/T, MMP-9-1562 C/T, MMP-13-77A/G, TNF-α-308 G/A,CCR5-?32), and serum levels of MMPs(2, 3, 8, 9 and 10) and TIMPs(1, 2 and 4) were assessed. Liver fibrosis was determined by transient elastometry, although other non-invasive markers of fibrosis were also considered. Significant liver fibrosis(F ≥ 2) was defined by a transient elastometry value ≥ 7.1 kP a.RESULTS A total of 34 patients(21.5%) had liver fibrosis ≥ F2. MMP-2 and TIMP-2 serum levels were higher in patients with liver fibrosis ≥ F2(P = 0.02 and P = 0.03, respectively) and correlated positively with transient elastometry values(P = 0.02 and P = 0.0009, respectively), whereas MMP-9 values were negatively correlated with transient elastometry measurements(P = 0.01). Multivariate analyses showed that high levels of MMP-2(OR = 2.397; 95%CI: 1.191-4.827, P = 0.014) were independently associated with liver fibrosis ≥ F2 in the patients as a whole. MMP-2(OR = 7.179; 95%CI: 1.210-42.581, P = 0.03) and male gender(OR = 10.040; 95%CI: 1.621-62.11, P = 0.013) were also independent predictors of fibrosis ≥ F2 in the HCV-infected subgroup. Likewise, MMP-2, TIMP-2 and MMP-9 were independently associated with transient elastometry values and other non-invasive markers of liver fibrosis. None of the six SNPs evaluated had any significant association with liver fibrosis ≥ F2.CONCLUSION Certain MMPs and TIMPs, particularly MMP-2, seems to be associated with non-alcoholic liver fibrosis in HIVinfected patients with/without HCV coinfec

关键词： Human immunodeficiency virus Hepatitis C virus Liver fibrosis Transient elastometry Noninvasive fibrosis markers metalloproteases Their tissue inhibitors Genetic polymorphisms

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TIMP-1 and its potential diagnostic and prognostic value in pulmonary diseases

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2023年第2期1卷 67-76页

作者： Sultan Almuntashiri Abdullah Alhumaid Yin Zhu Yohan Han Saugata Dutta Ohmed Khilji Duo Zhang Xiaoyun Wang Clinical and Experimental Therapeutics Department of Clinical and Administrative PharmacyCollege of PharmacyUniversity of Georgia and Charlie Norwood VA Medical CenterAugustaGA 30912USA 2 Department of Clinical PharmacyCollege of PharmacyUniversity of HailHail 55473Saudi Arabia 3 Department of Emergency MedicineMedical College of GeorgiaAugusta UniversityAugustaGA 30912USA 4 Department of MedicineMedical College of GeorgiaAugusta UniversityAugustaGA 30912USA

Tissue inhibitors of metalloproteases(TIMPs)have caught the attention of many scientists due to their role in various physiological and pathological processes.TIMP-1,2,3,and 4 are known members of the TIMPs family.TIMPs exert their biological effects by,but are not limited to,inhibiting the activity of metalloproteases(MMPs).The balance between MMPs and TIMPs is critical for maintaining homeostasis of the extracellular matrix(ECM),while the imbalance between MMPs and TIMPs can lead to pathological changes,such as cancer.In this re-view,we summarized the current knowledge of TIMP-1 in several pulmonary diseases namely,acute lung injury(ALI)/acute respiratory distress syndrome(ARDS),pneumonia,asthma,chronic obstructive pulmonary disease(COPD),cystic fibrosis,and pulmonary fibrosis.Considering the potential of TIMP-1 serving as a non-invasive di-agnostic and/or prognostic biomarker,we also reviewed the circulating TIMP-1 levels in translational and clinical studies.

关键词： metalloproteases Extracellular matrix Chronic obstructive pulmonary disease Idiopathic pulmonary fibrosis Cystic fibrosis Lung injury

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Glioma associated microglia/macrophages, a potential pharmacological target to promote antitumor inflammatory immune response in the treatment of glioblastoma

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Neuroimmunology and Neuroinflammation 2018年第9期5卷 2-14页

作者： Cinzia Dello Russo Natalia Cappoli Institute of Pharmacology UniversitàCattolica del S CuoreRome00168Italy Fondazione Policlinico Gemelli IRCCS 00168RomeItaly

Glioma associated microglia/macrophages (GAMs) constitute the largest proportion of glioma infiltrating cells, par-ticularly in high grade tumors (i.e., glioblastoma). Once inside the tumors, GAMs usually acquire a specific pheno-type of activation that favors tumor growth, angiogenesis and promotes the invasion of normal brain parenchyma. Therefore, treatments that limit or prevent GAMs' recruitment at the tumor site or modulate their immune activa-tion promoting antitumor activities are expected to exert beneficial effects in glioblastoma. In the present paper, we aim at the revision of pharmacological strategies that interfere with GAMs' function and are currently proposed as an alternative/additional option to current approved cytotoxic regimens.

关键词： Glioblastoma macrophages microglia metalloproteases pro-inflammatory activation pro-tumor func-tions glioma associated microglia/macrophages targeted therapies pharmacotherapy

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