Hepatic stellate cells and astrocytes

Figures & data

Figure 1 Expression of GFAP in HSCs and astrocytes. Differentiation of HSCs into activated myofibroblasts (left) is a hallmark of fibrotic liver disease of different etiologies, such as viral hepatitis and chronic alcohol consumption.96 In chronic liver disease, perpetuation of HSC activation leads to excessive collagen and ECM deposition, resulting in liver fibrosis. Thus, sustained activation of HSCs is a target for the treatment of liver fibrosis.5 Astrocytes (right) become reactive in response to all forms of CNS injury or disease, causing cellular hypertrophy, scar formation and production of inhibitory CSPGs.6,7 CSPG removal from the injured CNS area offers promise for therapies to improve axonal regeneration after CNS injury.94

Figure 2 Dual role of HSCs and astrocytes in tissue repair. HSC activation and reactive astrogliosis after tissue injury each lead to deposition of growth factors, cytokines and ECM proteins that control cell survival, proliferation, growth and regeneration in an autocrine and paracrine manner. In both liver and CNS injury there is a dual role for HSC activation and reactive astrogliosis, respectively. The balance of protective and damaging effects of HSCs and astrocytes may be related to the mechanisms that regulate their cross-talk with hepatocytes and neurons, respectively; as well as the stage and context of injury.

Table 1 Functions of neuroglial-related molecules expressed in HSCs

Molecule	Functions	References
Expressed by HSCs:
p75^NTR	Differentiation	58, 17, 62
Neurotrophins (NGF, BDNF, NT-3, NT-4)	Apoptosis (NGF)	58, 62
Trk receptors (Trk B, Trk C)	Unknown	62
Hedgehog	Activation and viability	56
Glial fibrillary acidic protein (GFAP)	Unknown	1
Nestin	Unknown	97
Synemin	Unknown	98
Synaptophysin	Unknown	99
Neural cell adhesion molecule (NCAM)	Unknown	100
α-B-crystallin	Unknown	101
RhoN/Rnd2	Unknown	102, 103
Nucleotide receptors	Inhibition of cytosolic calcium signals and chemotaxis [A(2a) receptor]	104, 59
	Loss of actin stress fibers and inhibition of HSC contraction via Rho inhibition [A(2a) receptor]	105
Norepinephrine Dopamine Dopamine β-hydroxylase Tyrosine hydroxylase	Viability and proliferation, pro-fibrotic (Norepinephrine)	57
Serotonin (5-HT) Serotonin receptors Serotonin transporter (SERT)	Pro-fibrotic (5-HT)	106
Opioid receptors	Pro-fibrotic	107
Cannabinoid receptors	Pro-fibrotic (cannabinoid receptor 1)	108
		109
	Anti-fibrotic (cannabinoid receptor 2)	110
Induces a response in HSCs:
Acetylcholine	Proliferation and pro-fibrotic	111
Endocannabinoid	Necrosis on activated HSCs (Anandamide)	108
	Apoptosis on activated HSCs (2-AG)	112
Neuropeptide Y	Proliferation of activated HSCs	113

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