Stellate Cells and Portal Hypertension

Rockey, Don C.

doi:10.1016/b978-0-12-800134-9.00008-7

Cited by 3 publications

(4 citation statements)

References 113 publications

(148 reference statements)

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“…HSCs maintain liver's architecture by producing components of extracellular matrix (ECM), ECM‐degrading matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinase (TIMPs) (Campana & Iredale, 2015). HSCs regulate sinusoidal tone/blood flow by responding to vasoactive mediators such as endothelin‐1 (ET‐1), angiotensin, nitric oxide (NO), and prostaglandins (Rockey, 2015). During liver injury, the physiologically quiescent HSCs progressively lose retinoids and transdifferentiate into activated migratory myofibroblast‐like phenotype that expresses smooth muscle alpha‐actin (αSMA).…”

Section: Hepatic Stellate Cells (Hscs)mentioning

confidence: 99%

“…Expression of the potent fibrogenic cytokine transforming growth factor‐β (TGF‐β) and its receptors is increased in activated HSCs (aHSCs); TGF‐β, also secreted by KCs, monocyte‐derived macrophages and SECs, stimulates aHSCs to produce increasing amounts of ECM causing liver fibrosis and cirrhosis (Gandhi, 2017, 2020; Hasegawa et al, 2015; Krenkel & Tacke, 2017). Additionally, aHSCs can contribute significantly to portal hypertension due to increased expression of receptors for vasoconstrictors such as ET‐1 (Rockey, 2015). Thus, extensive investigations have been performed to develop strategies for selective elimination of aHSCs or their reversal to quiescence to treat fibrosis/cirrhosis (Hasegawa et al, 2015; Koyama et al, 2015; Oakley & Mann, 2015; Sherman, 2018; Tsuchida & Friedman, 2017).…”

Section: Hepatic Stellate Cells (Hscs)mentioning

confidence: 99%

“…Administration of LPS to rats increased expression of ET‐1 and its receptors as well as portal pressure, and pretreatment with an ET‐1 antagonist TAK‐044 reduced LPS‐induced increased portal pressure (Gandhi et al, 2001). Because ET‐1 causes contraction of HSCs (Housset et al, 1993; Kawada et al, 1993; Rockey, 2015; Zhang et al, 1994), and LPS upregulates ET‐1 and its receptors in HSCs (Gandhi et al, 2000), the autocrine action of ET‐1 on HSCs can be an important mechanism of liver injury. Thus, reduced upregulation of ET‐1 receptors in LPS‐administered HSC‐depleted mice compared to HSC‐sufficient mice (Stewart et al, 2014) is consistent with ET‐1/HSC interactions in endotoxemia.…”

Section: Hsc‐depletion Mouse Modelmentioning

confidence: 99%

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Stellate cell in hepatic inflammation and acute injury

Rani

Gandhi

2023

Journal Cellular Physiology

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The perisinusoidal hepatic stellate cells (HSCs) have been investigated extensively for their role as the major fibrogenic cells during chronic liver injury. HSCs also produce numerous cytokines, chemokines, and growth mediators, and express cell adhesion molecules constitutively and in response to stimulants such as endotoxin (lipopolysaccharide). With this property and by interacting with resident and recruited immune and inflammatory cells, HSCs regulate hepatic immune homeostasis, inflammation, and acute injury. Indeed, experiments with HSC-depleted animal models and cocultures have provided evidence for the prominent role of HSCs in the initiation and progression of inflammation and acute liver damage due to various toxic agents. Thus HSCs and/or mediators derived thereof during acute liver damage may be considered as potential therapeutic targets.

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Section: Hepatic Stellate Cells (Hscs)mentioning

confidence: 99%

Section: Hepatic Stellate Cells (Hscs)mentioning

confidence: 99%

Section: Hsc‐depletion Mouse Modelmentioning

confidence: 99%

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Stellate cell in hepatic inflammation and acute injury

Rani

Gandhi

2023

Journal Cellular Physiology

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“…This phenomenon leads to quiescent stellate cell activation, differentiation into activated myofibroblasts, and the release of endothelin-1 (ET-1), thromboxane A2, nitric oxide (NO), and prostaglandins. This process causes hepatic microcirculatory dysfunction and high portal pressure [45]. NO release induces the death of hepatocytes via necrosis or apoptosis, which also damages neighboring cells [46].…”

Section: Mechanism Underlying Gut-liver Axis Disruption In Aclfmentioning

confidence: 99%

Disruption of the gut-liver axis in the pathogenesis of acute-on-chronic liver failure

Zhang

Sun

et al. 2018

European Journal of Gastroenterology &Amp; Hepatology

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Acute-on-chronic liver failure (ACLF) is characterized by organ failure mediated by acute decompensation of cirrhosis. Recent studies have highlighted the importance of the gut-liver axis (GLS) and its association with ACLF pathogenesis. In this review, we discuss the mechanisms related to the alteration of the GLA and their involvement in ACLF pathogenesis and suggest some possible therapeutic options that could modulate the GLA dysfunction. This knowledge may provide information useful for the design of therapeutic strategies for gut dysbiosis and its complications in ACLF.

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Exploring Endogenous Tryptamines: Overlooked Agents Against Fibrosis in Chronic Disease? A Narrative Review

Korsmo

2024

Livers

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Long regarded as illicit substances with no clinical value, N-dimethylated tryptamines—such as N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, and bufotenine—have been found to produce naturally in a wide variety of species, including humans. Known for their psychoactive effects through serotonin receptors (5-HTRs), N-dimethylated tryptamines are currently being reinvestigated clinically for their long-term benefits in mental disorders. Endogenous tryptamine is methylated by indolethylamine-N-methyltransferase (INMT), which can then serve as an agonist to pro-survival pathways, such as sigma non-opioid intracellular receptor 1 (SIGMAR1) signaling. Fibrogenic diseases, like metabolic-associated fatty liver disease (MAFLD), steatohepatitis (MASH), and chronic kidney disease (CKD) have shown changes in INMT and SIGMAR1 activity in the progression of disease pathogenesis. At the cellular level, endothelial cells and fibroblasts have been found to express INMT in various tissues; however, little is known about tryptamines in endothelial injury and fibrosis. In this review, I will give an overview of the biochemistry, molecular biology, and current evidence of INMT’s role in hepatic fibrogenesis. I will also discuss current pre-clinical and clinical findings of N-methylated tryptamines and highlight new and upcoming therapeutic strategies that may be adapted for mitigating fibrogenic diseases. Finally, I will mention recent findings for mutualistic gut bacteria influencing endogenous tryptamine signaling and metabolism.

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Stellate Cells and Portal Hypertension

Cited by 3 publications

References 113 publications

Stellate cell in hepatic inflammation and acute injury

Stellate cell in hepatic inflammation and acute injury

Disruption of the gut-liver axis in the pathogenesis of acute-on-chronic liver failure

Exploring Endogenous Tryptamines: Overlooked Agents Against Fibrosis in Chronic Disease? A Narrative Review

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