Hepatic stellate cells and astrocytes: Stars of scar formation and tissue repair

Cell Cycle

Volumn 10, Issue 11, 2011, Pages 1764-1771

  Schachtrup, Christian ^a,d   Le Moan, Natacha ^a   Passino, Melissa A ^c,e   Akassoglou, Katerina ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c San Diego   (United States)

^d UNIVERSITY OF FREIBURG   (Germany)

^e ASTRAZENECA   (United Kingdom)

Author keywords

Chondroitin sulfate proteoglycans; Collagen; Epidermal growth factor; Extracellular matrix; Hepatocytes; Matrix metalloproteinases; Neurons; Neurotrophins; p75 neurotrophin receptor; Scar; Transforming growth factor

Indexed keywords

ALPHA SMOOTH MUSCLE ACTIN; BRAIN DERIVED NEUROTROPHIC FACTOR; BRAIN DERIVED NEUROTROPHIC FACTOR RECEPTOR; COLLAGEN TYPE 1; EPIDERMAL GROWTH FACTOR; EPIDERMAL GROWTH FACTOR RECEPTOR; FIBRIN; FIBRINOGEN; FIBROBLAST GROWTH FACTOR 2; GAMMA INTERFERON; GLIAL FIBRILLARY ACIDIC PROTEIN; HEPARIN BINDING EPIDERMAL GROWTH FACTOR; INTERLEUKIN 1; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; INTERLEUKIN 6; METALLOTHIONEIN; NERVE GROWTH FACTOR; NESTIN; NEUROTROPHIN 3 RECEPTOR; PROTEIN P75; SMAD2 PROTEIN; SMAD3 PROTEIN; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR SOX9; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA1; TRANSFORMING GROWTH FACTOR BETA2; TUMOR NECROSIS FACTOR ALPHA; UNINDEXED DRUG;

ASTROCYTE; ASTROCYTOSIS; BIOAVAILABILITY; BLOOD BRAIN BARRIER; BLOOD PRESSURE; BLOOD TISSUE HOMEOSTASIS; BLOOD VESSEL INJURY; BRAIN BLOOD FLOW; CELL ACTIVATION; CELL DEATH; CELL DIFFERENTIATION; CELL GROWTH; CELL PROLIFERATION; CELL SURVIVAL; FIBRINOGEN BLOOD LEVEL; GLIA CELL; GLIOSIS; HOMEOSTASIS; INFLAMMATION; LIVER FIBROSIS; LIVER REGENERATION; MYOFIBROBLAST; NERVE REGENERATION; NONHUMAN; PROTEIN PHOSPHORYLATION; REVIEW; SCAR FORMATION; SPINAL CORD INJURY; STELLATE CELL; STEM CELL; THERAPY; UPREGULATION;

EID: 79957914333     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.10.11.15828     Document Type: Review

References (113)

1. Gard AL, White FP, Dutton GR. Extra-neural glial fibrillary acidic protein (GFAP) immunoreactivity in perisinusoidal stellate cells of rat liver. J Neuroimmunol 1985; 8:359-75. (Pubitemid 15025262)
2. Buniatian GH, Hartmann HJ, Traub P, Weser U, Wiesinger H, Gebhardt R. Acquisition of blood-tissue barrier-supporting features by hepatic stellate cells and astrocytes of myofibroblastic phenotype. Inverse dynamics of metallothionein and glial fibrillary acidic protein expression. Neurochem Int 2001; 38:373-83.
3. Geerts A. History, heterogeneity, developmental biology and functions of quiescent hepatic stellate cells. Semin Liver Dis 2001; 21:311-35. (Pubitemid 32923763)
4. Geerts A, Niki T, Hellemans K, De Craemer D, Van Den Berg K, Lazou JM, et al. Purification of rat hepatic stellate cells by side scatter-activated cell sorting. Hepatology 1998; 27:590-8.
5. Bataller R, Brenner DA. Hepatic stellate cells as a target for the treatment of liver fibrosis. Semin Liver Dis 2001; 21:437-51. (Pubitemid 32923771)
6. Sofroniew MV. Reactive astrocytes in neural repair and protection. Neuroscientist 2005; 11:400-7. (Pubitemid 41339226)
7. Silver J, Miller JH. Regeneration beyond the glial scar. Nat Rev Neurosci 2004; 5:146-56. (Pubitemid 38160289)
8. Eddleston M, Mucke L. Molecular profile of reactive astrocytes - implications for their role in neurologic disease. Neuroscience 1993; 54:15-36. (Pubitemid 23147085)
9. Yoshida K, Gage FH. Cooperative regulation of nerve growth factor synthesis and secretion in fibroblasts and astrocytes by fibroblast growth factor and other cytokines. Brain Res 1992; 569:14-25.
10. Asada H, Ip NY, Pan L, Razack N, Parfitt MM, Plunkett RJ. Time course of ciliary neurotrophic factor mRNA expression is coincident with the presence of protoplasmic astrocytes in traumatized rat striatum. J Neurosci Res 1995; 40:22-30.
11. Wu VW, Schwartz JP. Cell culture models for reactive gliosis: new perspectives. J Neurosci Res 1998; 51:675-81. (Pubitemid 28144936)
12. Pinzani M. Novel insights into the biology and physiology of the Ito cell. Pharmacol Ther 1995; 66:387-412.
13. Taub R. Liver regeneration: from myth to mechanism. Nat Rev Mol Cell Biol 2004; 5:836-47. (Pubitemid 39336277)
14. Bush TG, Puvanachandra N, Horner CH, Polito A, Ostenfeld T, Svendsen CN, et al. Leukocyte infiltration, neuronal degeneration and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron 1999; 23:297-308. (Pubitemid 29315725)
15. Okada S, Nakamura M, Katoh H, Miyao T, Shimazaki T, Ishii K, et al. Conditional ablation of Stat3 or Socs3 discloses a dual role for reactive astrocytes after spinal cord injury. Nat Med 2006; 12:829-34. (Pubitemid 44050074)
16. Kalinichenko VV, Bhattacharyya D, Zhou Y, Gusarova GA, Kim W, Shin B, et al. Foxf1+/- mice exhibit defective stellate cell activation and abnormal liver regeneration following CCl4 injury. Hepatology 2003; 37:107-17. (Pubitemid 36042151)
17. Passino MA, Adams RA, Sikorski SL, Akassoglou K. Regulation of hepatic stellate cell differentiation by the neurotrophin receptor p75NTR. Science 2007; 315:1853-6. (Pubitemid 46580146)
18. Voskuhl RR, Peterson RS, Song B, Ao Y, Morales LB, Tiwari-Woodruff S, et al. Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS. J Neurosci 2009; 29:11511-22.
19. Gressner AM, Weiskirchen R. Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGFbeta as major players and therapeutic targets. J Cell Mol Med 2006; 10:76-99. (Pubitemid 44874293)
20. Hellerbrand C, Stefanovic B, Giordano F, Burchardt ER, Brenner DA. The role of TGFbeta1 in initiating hepatic stellate cell activation in vivo. J Hepatol 1999; 30:77-87. (Pubitemid 29023655)
21. Schnabl B, Kweon YO, Frederick JP, Wang XF, Rippe RA, Brenner DA. The role of Smad3 in mediating mouse hepatic stellate cell activation. Hepatology 2001; 34:89-100. (Pubitemid 32591487)
22. Uemura M, Swenson ES, Gaca MD, Giordano FJ, Reiss M, Wells RG. Smad2 and Smad3 play different roles in rat hepatic stellate cell function and alpha-smooth muscle actin organization. Mol Biol Cell 2005; 16:4214-24. (Pubitemid 41262890)
23. Wang Y, Moges H, Bharucha Y, Symes A. Smad3 null mice display more rapid wound closure and reduced scar formation after a stab wound to the cerebral cortex. Exp Neurol 2007; 203:168-84. (Pubitemid 44821175)
24. Lagord C, Berry M, Logan A. Expression of TGFbeta2 but not TGFbeta1 correlates with the deposition of scar tissue in the lesioned spinal cord. Mol Cell Neurosci 2002; 20:69-92. (Pubitemid 34634329)
25. Wyss-Coray T, Feng L, Masliah E, Ruppe MD, Lee HS, Toggas SM, et al. Increased central nervous system production of extracellular matrix components and development of hydrocephalus in transgenic mice overexpressing transforming growth factor-beta1. Am J Pathol 1995; 147:53-67.
26. Asher RA, Morgenstern DA, Fidler PS, Adcock KH, Oohira A, Braistead JE, et al. Neurocan is upregulated in injured brain and in cytokine-treated astrocytes. J Neurosci 2000; 20:2427-38. (Pubitemid 30220330)
27. Moon LD, Fawcett JW. Reduction in CNS scar formation without concomitant increase in axon regeneration following treatment of adult rat brain with a combination of antibodies to TGFbeta1 and beta2. Eur J Neurosci 2001; 14:1667-77. (Pubitemid 35478035)
28. Adams RA, Passino M, Sachs BD, Nuriel T, Akassoglou K. Fibrin mechanisms and functions in nervous system pathology. Mol Interv 2004; 4:163-76. (Pubitemid 38960845)
29. Adams RA, Schachtrup C, Davalos D, Tsigelny I, Akassoglou K. Fibrinogen signal transduction as a mediator and therapeutic target in inflammation: Lessons from Multiple Sclerosis. Curr Med Chem 2007; 14:2925-36. (Pubitemid 350201659)
30. Schachtrup C, Ryu JK, Helmrick MJ, Vagena E, Galanakis DK, Degen JL, et al. Fibrinogen triggers astrocyte scar formation by promoting the availability of active TGFbeta after vascular damage. J Neurosci 30:5843-54.
31. Ng VL, Sabla GE, Melin-Aldana H, Kelley-Loughnane N, Degen JL, Bezerra JA. Plasminogen deficiency results in poor clearance of non-fibrin matrix and persistent activation of hepatic stellate cells after an acute injury. J Hepatol 2001; 35:781-9. (Pubitemid 34717670)
32. Nieto N. Oxidative-stress and IL-6 mediate the fibrogenic effects of rodent Kupffer cells on stellate cells. Hepatology 2006; 44:1487-501. (Pubitemid 44953654)
33. Han YP, Zhou L, Wang J, Xiong S, Garner WL, French SW, et al. Essential role of matrix metalloproteinases in interleukin-1-induced myofibroblastic activation of hepatic stellate cell in collagen. J Biol Chem 2004; 279:4820-8. (Pubitemid 38199077)
34. Yu C, Wang F, Jin C, Huang X, Miller DL, Basilico C, et al. Role of fibroblast growth factor type 1 and 2 in carbon tetrachloride-induced hepatic injury and fibrogenesis. Am J Pathol 2003; 163:1653-62. (Pubitemid 37175112)
35. Herx LM, Yong VW. Interleukin-1beta is required for the early evolution of reactive astrogliosis following CNS lesion. J Neuropathol Exp Neurol 2001; 60:961-71. (Pubitemid 32924122)
36. Campbell IL, Abraham CR, Masliah E, Kemper P, Inglis JD, Oldstone MB, et al. Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci USA 1993; 90:10061-5. (Pubitemid 23328251)
37. Akassoglou K, Bauer J, Kassiotis G, Pasparakis M, Lassmann H, Kollias G, et al. Oligodendrocyte apoptosis and primary demyelination induced by local TNF/ p55TNF receptor signaling in the central nervous system of transgenic mice: models for multiple sclerosis with primary oligodendrogliopathy. Am J Pathol 1998; 153:801-13. (Pubitemid 28419033)
38. Penkowa M, Giralt M, Lago N, Camats J, Carrasco J, Hernandez J, et al. Astrocyte-targeted expression of IL-6 protects the CNS against a focal brain injury. Exp Neurol 2003; 181:130-48. (Pubitemid 36629235)
39. Mattson MP, Cheng B, Baldwin SA, Smith-Swintosky VL, Keller J, Geddes JW, et al. Brain injury and tumor necrosis factors induce calbindin D-28k in astrocytes: evidence for a cytoprotective response. J Neurosci Res 1995; 42:357-70.
40. Yong VW, Moumdjian R, Yong FP, Ruijs TC, Freedman MS, Cashman N, et al. Gamma-interferon promotes proliferation of adult human astrocytes in vitro and reactive gliosis in the adult mouse brain in vivo. Proc Natl Acad Sci USA 1991; 88:7016-20. (Pubitemid 21915080)
41. Reuss B, Dono R, Unsicker K. Functions of fibroblast growth factor (FGF)-2 and FGF-5 in astroglial differentiation and blood-brain barrier permeability: evidence from mouse mutants. J Neurosci 2003; 23:6404-12. (Pubitemid 36909865)
42. Liu B, Chen H, Johns TG, Neufeld AH. Epidermal growth factor receptor activation: an upstream signal for transition of quiescent astrocytes into reactive astrocytes after neural injury. J Neurosci 2006; 26:7532-40. (Pubitemid 44315222)
43. Smith GM, Strunz C. Growth factor and cytokine regulation of chondroitin sulfate proteoglycans by astrocytes. Glia 2005; 52:209-18. (Pubitemid 43076151)
44. Gris P, Tighe A, Levin D, Sharma R, Brown A. Transcriptional regulation of scar gene expression in primary astrocytes. Glia 2007; 55:1145-55. (Pubitemid 47204206)
45. Sofroniew MV. Molecular dissection of reactive astrogliosis and glial scar formation. Trends Neurosci 2009; 32:638-47.
46. Jin YL, Enzan H, Kuroda N, Hayashi Y, Nakayama H, Zhang YH, et al. Tissue remodeling following submassive hemorrhagic necrosis in rat livers induced by an intraperitoneal injection of dimethylnitrosamine. Virchows Arch 2003; 442:39-47. (Pubitemid 36216357)
47. Janzer RC, Raff MC. Astrocytes induce blood-brain barrier properties in endothelial cells. Nature 1987; 325:253-7. (Pubitemid 17049884)
48. Koehler RC, Roman RJ, Harder DR. Astrocytes and the regulation of cerebral blood flow. Trends Neurosci 2009; 32:160-9.
49. Thimgan MS, Yee HF Jr. Quantitation of rat hepatic stellate cell contraction: stellate cells' contribution to sinusoidal resistance. Am J Physiol 1999; 277:137-43.
50. Rockey DC, Weisiger RA. Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: implications for regulation of portal pressure and resistance. Hepatology 1996; 24:233-40. (Pubitemid 26249439)
51. Sato M, Suzuki S, Senoo H. Hepatic stellate cells: unique characteristics in cell biology and phenotype. Cell Struct Funct 2003; 28:105-12. (Pubitemid 36790453)
52. Magness ST, Bataller R, Yang L, Brenner DA. A dual reporter gene transgenic mouse demonstrates heterogeneity in hepatic fibrogenic cell populations. Hepatology 2004; 40:1151-9. (Pubitemid 39425571)
53. Friedman SL. Stellate cells: a moving target in hepatic fibrogenesis. Hepatology 2004; 40:1041-3. (Pubitemid 39425557)
54. Bioulac-Sage P, Lafon ME, Saric J, Balabaud C. Nerves and perisinusoidal cells in human liver. J Hepatol 1990; 10:105-12.
55. Rafuse VF, Soundararajan P, Leopold C, Robertson HA. Neuroprotective properties of cultured neural progenitor cells are associated with the production of sonic hedgehog. Neuroscience 2005; 131:899-916. (Pubitemid 40320942)
56. Sicklick JK, Li YX, Choi SS, Qi Y, Chen W, Bustamante M, et al. Role for hedgehog signaling in hepatic stellate cell activation and viability. Lab Invest 2005; 85:1368-80. (Pubitemid 41509385)
57. Oben JA, Roskams T, Yang S, Lin H, Sinelli N, Torbenson M, et al. Hepatic fibrogenesis requires sympathetic neurotransmitters. Gut 2004; 53:438-45. (Pubitemid 38241344)
58. Trim N, Morgan S, Evans M, Issa R, Fine D, Afford S, et al. Hepatic stellate cells express the low affinity nerve growth factor receptor p75 and undergo apoptosis in response to nerve growth factor stimulation. Am J Pathol 2000; 156:1235-43. (Pubitemid 30660002)
59. Hashmi AZ, Hakim W, Kruglov EA, Watanabe A, Watkins W, Dranoff JA, et al. Adenosine inhibits cytosolic calcium signals and chemotaxis in hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol 2007; 292:395-401.
60. Chao MV. Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci 2003; 4:299-309. (Pubitemid 37271375)
61. Lomen-Hoerth C, Shooter EM. Widespread Neurotrophin Receptor Expression in the Immune System and Other Nonneuronal Rat Tissues. Journal of Neurochemistry 1995; 64:1780-9.
62. Cassiman D, Denef C, Desmet VJ, Roskams T. Human and rat hepatic stellate cells express neurotrophins and neurotrophin receptors. Hepatology 2001; 33:148-58. (Pubitemid 32016897)
63. Oakley F, Trim N, Constandinou CM, Ye W, Gray AM, Frantz G, et al. Hepatocytes express nerve growth factor during liver injury: evidence for paracrine regulation of hepatic stellate cell apoptosis. Am J Pathol 2003; 163:1849-58. (Pubitemid 37310016)
64. Geerts A. The simple truth is seldom true and never simple: dual role for p75(NTR) in transdifferentation and cell death of hepatic stellate cells. Hepatology 2007; 46:600-1. (Pubitemid 47344797)
65. Zvibel I, Atias D, Phillips A, Halpern Z, Oren R. Thyroid hormones induce activation of rat hepatic stellate cells through increased expression of p75 neurotrophin receptor and direct activation of Rho. Lab Invest 2010; 90:674-84.
66. Trentin AG. Thyroid hormone and astrocyte morphogenesis. J Endocrinol 2006; 189:189-97.
67. Kendall TJ, Hennedige S, Aucott RL, Hartland SN, Vernon MA, Benyon RC, et al. p75 Neurotrophin receptor signaling regulates hepatic myofibroblast proliferation and apoptosis in recovery from rodent liver fibrosis. Hepatology 2009; 49:901-10.
68. Suzuki K, Tanaka M, Watanabe N, Saito S, Nonaka H, Miyajima A. p75 Neurotrophin receptor is a marker for precursors of stellate cells and portal fibroblasts in mouse fetal liver. Gastroenterology 2008; 135:270-81 3.
69. Yamashita T, Tohyama M. The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI. Nat Neurosci 2003; 6:461-7. (Pubitemid 36514693)
70. Hutton LA, deVellis J, Perez-Polo JR. Expression of p75NGFR TrkA and TrkB mRNA in rat C6 glioma and type I astrocyte cultures. J Neurosci Res 1992; 32:375-83.
71. Cragnolini AB, Huang Y, Gokina P, Friedman WJ. Nerve growth factor attenuates proliferation of astrocytes via the p75 neurotrophin receptor. Glia 2009; 57:1386-92.
72. Rudge JS, Li Y, Pasnikowski EM, Mattsson K, Pan L, Yancopoulos GD, et al. Neurotrophic factor receptors and their signal transduction capabilities in rat astrocytes. Eur J Neurosci 1994; 6:693-705. (Pubitemid 24143917)
73. NTR immunoreactivity in the rat dentate gyrus is mostly within presynaptic profiles but is also found in some astrocytic and postsynaptic profiles. J Comp Neurol 1999; 407:77-91.
74. Hanbury R, Charles V, Chen EY, Leventhal L, Rosenstein JM, Mufson EJ, et al. Excitotoxic and metabolic damage to the rodent striatum: role of the p75 neurotrophin receptor and glial progenitors. J Comp Neurol 2002; 444:291-305. (Pubitemid 34194918)
75. Oderfeld-Nowak B, Orzylowska-Sliwinska O, Soltys Z, Zaremba M, Januszewski S, Janeczko K, et al. Concomitant upregulation of astroglial high and low affinity nerve growth factor receptors in the CA1 hippocampal area following global transient cerebral ischemia in rat. Neuroscience 2003; 120:31-40. (Pubitemid 36782629)
76. NTR- mediated apoptosis via neurotrophin receptor-interacting factor in hippocampal neurons after seizures. J Neurosci 2008; 28:9870-9.
77. NTR in glia. Trends Neurosci 2008; 31:99-104.
78. Giuliani A, D'Intino G, Paradisi M, Giardino L, Calza L. p75(NTR)-immunoreactivity in the subventricular zone of adult male rats: expression by cycling cells. J Mol Histol 2004; 35:749-58. (Pubitemid 41404620)
79. Johnston AL, Lun X, Rahn JJ, Liacini A, Wang L, Hamilton MG, et al. The p75 neurotrophin receptor is a central regulator of glioma invasion. PLoS Biol 2007; 5:212.
80. Wang L, Rahn JJ, Lun X, Sun B, Kelly JJ, Weiss S, et al. Gamma-secretase represents a therapeutic target for the treatment of invasive glioma mediated by the p75 neurotrophin receptor. PLoS Biol 2008; 6:289.
81. Herrmann JL, Menter DG, Hamada J, Marchetti D, Nakajima M, Nicolson GL. Mediation of NGF-stimulated extracellular matrix invasion by the human melanoma low-affinity p75 neurotrophin receptor: melanoma p75 functions independently of trkA. Mol Biol Cell 1993; 4:1205-16. (Pubitemid 24007581)
82. Shonukan O, Bagayogo I, McCrea P, Chao M, Hempstead B. Neurotrophin-induced melanoma cell migration is mediated through the actin-bundling protein fascin. Oncogene 2003; 22:3616-23. (Pubitemid 36765321)
83. Walch ET, Albino AP, Marchetti D. Correlation of overexpression of the low-affinity p75 neurotrophin receptor with augmented invasion and heparanase production in human malignant melanoma cells. Int J Cancer 1999; 82:112-20. (Pubitemid 29266115)
84. Denkins Y, Reiland J, Roy M, Sinnappah-Kang ND, Galjour J, Murry BP, et al. Brain metastases in melanoma: roles of neurotrophins. Neuro Oncol 2004; 6:154-65. (Pubitemid 38455762)
85. Uyama N, Shimahara Y, Kawada N, Seki S, Okuyama H, Iimuro Y, et al. Regulation of cultured rat hepatocyte proliferation by stellate cells. J Hepatol 2002; 36:590-9. (Pubitemid 34506239)
86. Mabuchi A, Mullaney I, Sheard P, Hessian P, Zimmermann A, Senoo H, et al. Role of Hepatic Stellate Cells in the Early Phase of Liver Regeneration in Rat: Formation of Tight Adhesion to Parenchymal Cells. Comp Hepatol 2004; 3:29.
87. Mabuchi A, Mullaney I, Sheard PW, Hessian PA, Mallard BL, Tawadrous MN, et al. Role of hepatic stellate cell/hepatocyte interaction and activation of hepatic stellate cells in the early phase of liver regeneration in the rat. J Hepatol 2004; 40:910-6. (Pubitemid 38670124)
88. Krieglstein K, Strelau J, Schober A, Sullivan A, Unsicker K. TGFbeta and the regulation of neuron survival and death. J Physiol Paris 2002; 96:25-30. (Pubitemid 34087030)
89. Brionne TC, Tesseur I, Masliah E, Wyss-Coray T. Loss of TGFbeta1 leads to increased neuronal cell death and microgliosis in mouse brain. Neuron 2003; 40:1133-45. (Pubitemid 38032790)
90. Rudge JS. Astrocyte-derived neurotrophic factors. In: Murphy S, ed. Astrocytes: pharmacology and function: New York: Academic 1993; 267-305.
91. Herrmann JE, Imura T, Song B, Qi J, Ao Y, Nguyen TK, et al. STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. J Neurosci 2008; 28:7231-43.
92. Lu P, Yang H, Jones LL, Filbin MT, Tuszynski MH. Combinatorial therapy with neurotrophins and cAMP promotes axonal regeneration beyond sites of spinal cord injury. J Neurosci 2004; 24:6402-9. (Pubitemid 38944231)
93. Kadoya K, Tsukada S, Lu P, Coppola G, Geschwind D, Filbin MT, et al. Combined intrinsic and extrinsic neuronal mechanisms facilitate bridging axonal regeneration one year after spinal cord injury. Neuron 2009; 64:165-72.
94. Cafferty WB, Yang SH, Duffy PJ, Li S, Strittmatter SM. Functional axonal regeneration through astrocytic scar genetically modified to digest chondroitin sulfate proteoglycans. J Neurosci 2007; 27:2176-85. (Pubitemid 46340954)
95. Tsukamoto H, She H, Hazra S, Cheng J, Miyahara T. Anti-adipogenic regulation underlies hepatic stellate cell transdifferentiation. J Gastroenterol Hepatol 2006; 21:102-5.
96. Kisseleva T, Brenner DA. Hepatic stellate cells and the reversal of fibrosis. J Gastroenterol Hepatol 2006; 21:84-7.
97. Niki T, Pekny M, Hellemans K, Bleser PD, Berg KV, Vaeyens F, et al. Class VI intermediate filament protein nestin is induced during activation of rat hepatic stellate cells. Hepatology 1999; 29:520-7.
98. Uyama N, Zhao L, Van Rossen E, Hirako Y, Reynaert H, Adams DH, et al. Hepatic stellate cells express synemin, a protein bridging intermediate filaments to focal adhesions. Gut 2006; 55:1276-89. (Pubitemid 44277359)
99. Cassiman D, van Pelt J, De Vos R, Van Lommel F, Desmet V, Yap SH, et al. Synaptophysin: A novel marker for human and rat hepatic stellate cells. Am J Pathol 1999; 155:1831-9.
100. Knittel T, Aurisch S, Neubauer K, Eichhorst S, Ramadori G. Cell-type-specific expression of neural cell adhesion molecule (N-CAM) in Ito cells of rat liver. Upregulation during in vitro activation and in hepatic tissue repair. Am J Pathol 1996; 149:449-62. (Pubitemid 26256333)
101. Lang A, Schrum LW, Schoonhoven R, Tuvia S, Solis-Herruzo JA, Tsukamoto H, et al. Expression of small heat shock protein alphaB-crystallin is induced after hepatic stellate cell activation. Am J Physiol Gastrointest Liver Physiol 2000; 279:1333-42.
102. Nishi M, Takeshima H, Houtani T, Nakagawara K, Noda T, Sugimoto T. RhoN, a novel small GTP-binding protein expressed predominantly in neurons and hepatic stellate cells. Brain Res Mol Brain Res 1999; 67:74-81. (Pubitemid 29170070)
103. Chardin P. Function and regulation of Rnd proteins. Nat Rev Mol Cell Biol 2006; 7:54-62. (Pubitemid 43361572)
104. Dranoff JA, Ogawa M, Kruglov EA, Gaca MD, Sevigny J, Robson SC, et al. Expression of P2Y nucleotide receptors and ectonucleotidases in quiescent and activated rat hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol 2004; 287:417-24.
105. Sohail MA, Hashmi AZ, Hakim W, Watanabe A, Zipprich A, Groszmann RJ, et al. Adenosine induces loss of actin stress fibers and inhibits contraction in hepatic stellate cells via Rho inhibition. Hepatology 2009; 49:185-94.
106. Ruddell RG, Oakley F, Hussain Z, Yeung I, Bryan-Lluka LJ, Ramm GA, et al. A role for serotonin (5-HT) in hepatic stellate cell function and liver fibrosis. Am J Pathol 2006; 169:861-76. (Pubitemid 44411953)
107. Ebrahimkhani MR, Kiani S, Oakley F, Kendall T, Shariftabrizi A, Tavangar SM, et al. Naltrexone, an opioid receptor antagonist, attenuates liver fibrosis in bile duct ligated rats. Gut 2006; 55:1606-16. (Pubitemid 44629212)
108. Siegmund SV, Uchinami H, Osawa Y, Brenner DA, Schwabe RF. Anandamide induces necrosis in primary hepatic stellate cells. Hepatology 2005; 41:1085-95. (Pubitemid 40593916)
109. Teixeira-Clerc F, Julien B, Grenard P, Tran Van Nhieu J, Deveaux V, Li L, et al. CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. Nat Med 2006; 12:671-6. (Pubitemid 43865236)
110. Julien B, Grenard P, Teixeira-Clerc F, Van Nhieu JT, Li L, Karsak M, et al. Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology 2005; 128:742-55. (Pubitemid 40585376)
111. Oben JA, Yang S, Lin H, Ono M, Diehl AM. Acetylcholine promotes the proliferation and collagen gene expression of myofibroblastic hepatic stellate cells. Biochem Biophys Res Commun 2003; 300:172-7. (Pubitemid 36042947)
112. Siegmund SV, Qian T, de Minicis S, Harvey-White J, Kunos G, Vinod KY, et al. The endocannabinoid 2-arachidonoyl glycerol induces death of hepatic stellate cells via mitochondrial reactive oxygen species. FASEB J 2007; 21:2798-806. (Pubitemid 47372747)
113. Oben JA, Yang S, Lin H, Ono M, Diehl AM. Norepinephrine and neuropeptide Y promote proliferation and collagen gene expression of hepatic myofibroblastic stellate cells. Biochem Biophys Res Commun 2003; 302:685-90. (Pubitemid 36294027)