Nerves and perisinusoidal cells in human liver

Bioulac‐Sage, Paulette; Lafon, Marie‐Edith; Saric, Jean; Balabaud, Charles

doi:10.1016/0168-8278(90)90080-b

Cited by 142 publications

(96 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…24 Nerve endings are found in the liver close to HSCs, and HSCs in situ respond to perivascular nerve stimulation with a release of the osmolyte myoinositol and exhibit Ca 2ϩ signals in response to phenylephrin. [34][35][36] Stimulation with noradrenaline, the neurotransmitter of the peripheral sympathetic nervous system, results in a rapid release of prostaglandin F 2␣ and prostaglandin D 2 by freshly isolated HSCs. These prostaglandins activate the glycogenolysis in the neighboring parenchymal cells.…”

Section: Discussionmentioning

confidence: 99%

The niche of stellate cells within rat liver

et al. 2009

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

The niche of stellate cells within rat liver

et al. 2009

View full text Add to dashboard Cite

“…The autonomic nervous system also may influence on stellate cell contraction. It is known that neurons of the coeliac plexus terminate on stellate cells (Bioulac-Sage et al, 1990). Also, in common with brain astrocytes, stellate cells display glial fibrillar acidic protein (Buniatian et al, 1996;Neubauer et al, 1996) and the neural crest marker, nestin .…”

Section: Contractionmentioning

confidence: 99%

Chronic liver injury, TGF-β, and cancer

Bissell

2001

Exp Mol Med

155

View full text Add to dashboard Cite

Cells termed myofibroblasts are prominent in the injury response of all epithelial tissues. They exhibit proliferation, migration, production of collagen and other extracellular matrix (ECM) molecules, and contraction, all for containing the injury and closing the wound. When the injury is limited in time, the final stage of the repair involves a dismantling of the cellular apparatus and restoration of normal tissue structure. With multiple cycles of repair, however, there is net accumulation of ECM, to the detriment of tissue structure and function. Repair-related ECM coalesces into fibrous bundles and, over time, undergoes changes that render it resistant to degradation. The result is a scar. In the skin, a scar may have cosmetic importance only. In the liver, however, extensive scarring is the setting for unregulated growth and neoplasia; also, fibrous bands disrupt normal blood flow, leading to portal hypertension and its complications. With regard to therapy for fibrosis, the first consideration is elimination of the injury factor. However, given that many liver diseases do not have effective therapies at present, strategies targeting fibrogenesis per se are under development. The main source of myofibroblast-like cells and ECM production in the liver is the perisinusoidal stellate cell, which responds to injury with a pleiotypic change termed activation. Activation is orchestrated by cytokines and the ECM itself. Among the cytokines involved in this process, transforming growth factor-beta (TGF-β) is particularly prominent. The early changes in ECM include de novo production of a specific "fetal" isoform of fibronectin, which arises from sinusoidal endothelial cells. It is stimulated by TGF-β and acts directly on stellate cells to promote their activation. Based on these and other advances in understanding the fundamentals of the injury response, several strategies now exist for altering fibrogenesis, ranging from agents that block TGF-β to traditional Chinese herbal extracts. Arrest of fibrogenesis, even with underlying cirrhosis, is likely to extend life or prolong the time to transplant. Whether it reduces the risk of hepatocellular carcinoma remains to be proven. Although TGF-β antagonists are effective anti-fibrogenic agents, they will require detailed safety testing because of the finding that several forms of epithelial neoplasia are associated with altered regulation of TGF-β.

show abstract

“…Hepatic stellate cells (HSCs) are located in the spaces of Disse in close contact with hepatocytes, sinusoidal endothelial cells, and autonomic nerve fibers (3). A critical role of activated HSCs in collagen and extracellular matrix production has been previously observed.…”

mentioning

confidence: 99%

“…A critical role of activated HSCs in collagen and extracellular matrix production has been previously observed. HSC activation is characterized as a shift from the quiescent "storing" phenotype to the highly proliferative "myofibroblast-like" phenotype (4) and leads to increased fibrillar extracellular matrix production with reduced capabilities for degradation and remodeling (3). Several proinflammatory mediators are secreted from the activated HSCs, leading to further amplification of the inflammatory process (4,5).…”

mentioning

confidence: 99%

IL-17A Plays a Critical Role in the Pathogenesis of Liver Fibrosis through Hepatic Stellate Cell Activation

Tan

Qian

Jiang

et al. 2013

The Journal of Immunology

269

208

View full text Add to dashboard Cite

Liver fibrosis is a severe, life-threatening clinical condition resulting from nonresolving hepatitis of different origins. IL-17A is critical in inflammation, but its relation to liver fibrosis remains elusive. We find increased IL-17A expression in fibrotic livers from HBV-infected patients undergoing partial hepatectomy because of cirrhosis-related early-stage hepatocellular carcinoma in comparison with control nonfibrotic livers from uninfected patients with hepatic hemangioma. In fibrotic livers, IL-17A immunoreactivity localizes to the inflammatory infiltrate. In experimental carbon tetrachloride–induced liver fibrosis of IL-17RA–deficient mice, we observe reduced neutrophil influx, proinflammatory cytokines, hepatocellular necrosis, inflammation, and fibrosis as compared with control C57BL/6 mice. IL-17A is produced by neutrophils and T lymphocytes expressing the Th17 lineage–specific transcription factor Retinoic acid receptor–related orphan receptor γt. Furthermore, hepatic stellate cells (HSCs) isolated from naive C57BL/6 mice respond to IL-17A with increased IL-6, α-smooth muscle actin, collagen, and TGF-β mRNA expression, suggesting an IL-17A–driven fibrotic process. Pharmacologic ERK1/2 or p38 inhibition significantly attenuated IL-17A–induced HSC activation and collagen expression. In conclusion, IL-17A+ Retinoic acid receptor–related orphan receptor γt+ neutrophils and T cells are recruited into the injured liver driving a chronic, fibrotic hepatitis. IL-17A–dependent HSC activation may be critical for liver fibrosis. Thus, blockade of IL-17A could potentially benefit patients with chronic hepatitis and liver fibrosis.

show abstract

Nerves and perisinusoidal cells in human liver

Cited by 142 publications

References 15 publications

The niche of stellate cells within rat liver

The niche of stellate cells within rat liver

Chronic liver injury, TGF-β, and cancer

IL-17A Plays a Critical Role in the Pathogenesis of Liver Fibrosis through Hepatic Stellate Cell Activation

Contact Info

Product

Resources

About