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      Herba Artemisiae Capillaris Extract Prevents the Development of Streptozotocin-Induced Diabetic Nephropathy of Rat

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          Abstract

          Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world; until now there is no specific drug available. In this work, we use herba artemisiae capillaris extract (HACE) to alleviate renal fibrosis characterized by the excessive accumulation of extracellular matrix (ECM) in rats, aiming to investigate the protective effect of the HACE on DN. We found that the intragastric treatment of high-dose HACE could reverse the effect of streptozotocin not only to decrease the level of blood glucose and blood lipid in different degree but also further to improve renal functions. It is worth mentioning that the effect of HACE treatment was comparable to the positive drug benazepril. Moreover, we found that HACE treatment could on one hand inhibit oxidative stress in DN rats through regulating enzymatic activity for scavenging reactive oxygen species and on the other hand increase the ECM degradation through regulating the activity of metalloproteinase-2 (MMP-2) and the expression of tissue transglutaminase (tTG), which explained why HACE treatment inhibited ECM accumulation. On the basis of above experimental results, we conclude that HACE prevents DN development in a streptozotocin-induced DN rat model, and HACE is a promising candidate to cure DN in clinic.

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          Most cited references37

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          Transglutaminases: crosslinking enzymes with pleiotropic functions.

          Blood coagulation, skin-barrier formation, hardening of the fertilization envelope, extracellular-matrix assembly and other important biological processes are dependent on the rapid generation of covalent crosslinks between proteins. These reactions--which are catalysed by transglutaminases--endow the resulting supramolecular structure with extra rigidity and resistance against proteolytic degradation. Some transglutaminases function as molecular switches in cytoskeletal scaffolding and modulate protein-protein interactions. Having knowledge of these enzymes is essential for understanding the aetiologies of diverse hereditary diseases of the blood and skin, and various autoimmune, inflammatory and degenerative conditions.
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            PAI-1 in tissue fibrosis.

            Fibrosis is defined as a fibroproliferative or abnormal fibroblast activation-related disease. Deregulation of wound healing leads to hyperactivation of fibroblasts and excessive accumulation of extracellular matrix (ECM) proteins in the wound area, the pathological manifestation of fibrosis. The accumulation of excessive levels of collagen in the ECM depends on two factors: an increased rate of collagen synthesis and or decreased rate of collagen degradation by cellular proteolytic activities. The urokinase/tissue type plasminogen activator (uPA/tPA) and plasmin play significant roles in the cellular proteolytic degradation of ECM proteins and the maintenance of tissue homeostasis. The activities of uPA/tPA/plasmin and plasmin-dependent MMPs rely mostly on the activity of a potent inhibitor of uPA/tPA, plasminogen activator inhibitor-1 (PAI-1). Under normal physiologic conditions, PAI-1 controls the activities of uPA/tPA/plasmin/MMP proteolytic activities and thus maintains the tissue homeostasis. During wound healing, elevated levels of PAI-1 inhibit uPA/tPA/plasmin and plasmin-dependent MMP activities, and, thus, help expedite wound healing. In contrast to this scenario, under pathologic conditions, excessive PAI-1 contributes to excessive accumulation of collagen and other ECM protein in the wound area, and thus preserves scarring. While the level of PAI-1 is significantly elevated in fibrotic tissues, lack of PAI-1 protects different organs from fibrosis in response to injury-related profibrotic signals. Thus, PAI-1 is implicated in the pathology of fibrosis in different organs including the heart, lung, kidney, liver, and skin. Paradoxically, PAI-1 deficiency promotes spontaneous cardiac-selective fibrosis. In this review, we discuss the significance of PAI-1 in the pathogenesis of fibrosis in multiple organs. Copyright © 2011 Wiley Periodicals, Inc.
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              Extracellular matrix metabolism in diabetic nephropathy.

              Diabetic nephropathy is characterized by excessive deposition of extracellular matrix proteins in the mesangium and basement membrane of the glomerulus and in the renal tubulointerstitium. This review summarizes the main changes in protein composition of the glomerular mesangium and basement membrane and the evidence that, in the mesangium, these are initiated by changes in glucose metabolism and the formation of advanced glycation end products. Both processes generate reactive oxygen species (ROS). The review includes discussion of how ROS may activate intracellular signaling pathways leading to the activation of redox-sensitive transcription factors. This in turn leads to change in the expression of genes encoding extracellular matrix proteins and the protease systems responsible for their turnover.
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                Author and article information

                Contributors
                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi
                1741-427X
                1741-4288
                2018
                14 February 2018
                : 2018
                : 5180165
                Affiliations
                1Institute of Virology and AIDS, The First Hospital of Jilin University, Jilin University, Dongminzhu Street 519, Changchun 130000, China
                2Department of Experimental Pharmacology and Toxicology, School of Pharmacy, Jilin University, Fujin Road 1266, Changchun 130021, China
                3Acupuncture Department, The Affiliated Hospital to Changchun University of Chinese Medicine, 1478 Gongnong Road, Changchun 130021, China
                4Department of Pharmacology, College of Basic Medical Science, Jilin University, Xinmin Street 126, Changchun 130021, China
                5Department of Obstetrics Gynecology, The Second Hospital of Jilin University, Ziqiang Street 218, Changchun 130041, China
                Author notes

                Academic Editor: Youn C. Kim

                Author information
                http://orcid.org/0000-0002-4427-0390
                http://orcid.org/0000-0001-5641-1675
                http://orcid.org/0000-0002-0512-6740
                http://orcid.org/0000-0003-2771-3425
                http://orcid.org/0000-0001-8082-7865
                http://orcid.org/0000-0001-8659-6543
                http://orcid.org/0000-0001-8444-4327
                Article
                10.1155/2018/5180165
                5832121
                5e7241e2-7c7b-4b87-b9d9-642d53e14038
                Copyright © 2018 Jianan Geng et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 August 2017
                : 1 December 2017
                : 26 December 2017
                Funding
                Funded by: Science and Technology Development Plan of Jilin Province
                Award ID: 20160101206JC
                Funded by: National Natural Science Foundation of China
                Award ID: 81302818
                Categories
                Research Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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