Kupffer-derived matrix metalloproteinase-9 contributes to liver fibrosis resolution

Feng, Min; Ding, Jie; Wang, Min; Zhang, Jie; Zhu, Xinhua; Guan, Wenxian

doi:10.7150/ijbs.25589

Cited by 67 publications

(50 citation statements)

References 23 publications

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“…IL-5also plays an important role in promoting tissue fibrosis [60,62]; and TNF antagonists are beneficial for the treatment of fibrotic disorders, supporting a pro-fibrotic role of TNF [41,[63][64][65]. By contrast, the role of MMP9 is unclear, having a pro-fibrotic or anti-fibrotic action in different rodent models [66,67]. Some anti-fibrotic factors, namely SMAD6, SMAD7, STAT1, and HGF, were also induced by the virus infection, although to a lesser extent compared to pro-fibrotic upregulation, perhaps as a counterbalance of the potent pro-fibrotic expression induced in vitro by virus infection.…”

Section: Discussionmentioning

confidence: 99%

HHV-6A Infection and Systemic Sclerosis: Clues of a Possible Association

et al. 2019

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Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, excessive extracellular matrix deposition, and fibrosis of the skin and internal organs. Several infectious agents, including human herpesvirus-6 (HHV-6), have been suggested as possible triggering factors, but a direct association is still missing. We characterized 26 SSc patients for the presence of HHV-6 in tissues and blood, the anti-HHV-6 response, HLA-G plasma levels, and KIR typing. Given the prominent role of endothelial cells (EC) in SSc pathogenesis, along with HHV-6 tropism for EC, we also investigated the expression of pro-fibrosis factors in HHV-6 infected EC. Results showed the presence of HHV-6A in skin biopsies, and an increased virus load was associated with disease severity and poor natural killer (NK) response against the virus, particularly in subjects exhibiting a KIR2 phenotype. HLA-G plasma levels were significantly higher in HHV-6A/B-KIR2 positive SSc patients and in vitro HHV-6A infection-induced pro-fibrosis factors expression in EC, supporting its role in the development of the fibrosing process. Our data suggest an association between virus infection/reactivation and disease, opening the way to future studies to understand the mechanisms by which HHV-6A might contribute to the multifactorial pathogenesis of SSc.

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Section: Discussionmentioning

confidence: 99%

HHV-6A Infection and Systemic Sclerosis: Clues of a Possible Association

et al. 2019

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“…Studies of CLDN treatment in wild-type mice or diphtheria toxin (DT)induced macrophage depletion in CD11b-DT receptor transgenic mice during fibrosis resolution demonstrate that a loss of macrophages results in delayed resolution of fibrosis and reduced hepatic expression of MMP9 and MMP13. 156,157 Moreover, adoptive transfer of wild-type KCs relieves fibrolysis in MMP9deficient mice. 156 Role of macrophages in physiological and pathological repair Liver repair and regeneration.…”

Section: Roles Of Macrophages In Resolving Inflammation During Liver mentioning

confidence: 99%

Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

et al. 2020

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Macrophages, which are key cellular components of the liver, have emerged as essential players in the maintenance of hepatic homeostasis and in injury and repair processes in acute and chronic liver diseases. Upon liver injury, resident Kupffer cells (KCs) sense disturbances in homeostasis, interact with hepatic cell populations and release chemokines to recruit circulating leukocytes, including monocytes, which subsequently differentiate into monocyte-derived macrophages (MoMϕs) in the liver. Both KCs and MoMϕs contribute to both the progression and resolution of tissue inflammation and injury in various liver diseases. The diversity of hepatic macrophage subsets and their plasticity explain their different functional responses in distinct liver diseases. In this review, we highlight novel findings regarding the origins and functions of hepatic macrophages and discuss the potential of targeting macrophages as a therapeutic strategy for liver disease.

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“…Abundant ROS are produced from mitochondria, and microsomes in parenchymal cells by regulating PPARα-associated signaling pathways. In addition, in Kupffer cells, the hepatic oxygen sensor and resident liver macrophage, has been postulated to trigger the formation of hepatic fibrosis by excessive ROS-induced apoptosis and inflammation [ 13 ]. Both hepatic stellate and endothelial cells are all specialized in producing ROS in physiological and pathological systems, and accustomed to suffering from lipid peroxidation [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study

Zhang

Wang

et al. 2018

IJMS

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Oxidative stress, defined as a disequilibrium between pro-oxidants and antioxidants, can result in histopathological lesions with a broad spectrum, ranging from asymptomatic hepatitis to hepatocellular carcinoma in an orchestrated manner. Although cells are equipped with sophisticated strategies to maintain the redox biology under normal conditions, the abundance of redox-sensitive xenobiotics, such as medicinal ingredients originated from herbs or animals, can dramatically invoke oxidative stress. Growing evidence has documented that the hepatotoxicity can be triggered by traditional Chinese medicine (TCM) during treating various diseases. Meanwhile, TCM-dependent hepatic disorder represents a strong correlation with oxidative stress, especially the persistent accumulation of intracellular reactive oxygen species. Of note, since TCM-derived compounds with their modulated targets are greatly diversified among themselves, it is complicated to elaborate the potential pathological mechanism. In this regard, data mining approaches, including network pharmacology and bioinformatics enrichment analysis have been utilized to scientifically disclose the underlying pathogenesis. Herein, top 10 principal TCM-modulated targets for oxidative hepatotoxicity including superoxide dismutases (SOD), malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), glutathione peroxidase (GPx), Bax, caspase-3, Bcl-2, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and nitric oxide (NO) have been identified. Furthermore, hepatic metabolic dysregulation may be the predominant pathological mechanism involved in TCM-induced hepatotoxic impairment.

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Kupffer-derived matrix metalloproteinase-9 contributes to liver fibrosis resolution

Cited by 67 publications

References 23 publications

HHV-6A Infection and Systemic Sclerosis: Clues of a Possible Association

HHV-6A Infection and Systemic Sclerosis: Clues of a Possible Association

Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study

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