[Role of stellate cells in alcoholic liver fibrosis].
Many different diseases and toxins can cause liver damage, which is difficult to treat and often leads to the development of liver fibrosis or even cirrhosis. The key event in this process is the activation of hepatic stellate cells (HSCs). During such activation, HSCs undergo a dramatic transformation in morphology and behavior, changing from a neuronal-like to a fibroblast-like morphology. After activation, HSCs increase their proliferation rate and extracellular matrix (ECM)production. Overproduction of ECM, which contains mainly collagen type I, is a direct cause of liver disruption. HSCs also produce substances which inhibit protease activities, such as TIMPs,which enhance ECM deposition in the liver. On the molecular level, HSCs are activated by cytokines,growth factors, and oxidative stress, which are abundant in afflicted liver. These factors induce intracellular signals transmitted by many kinases, the most important of which are JNK,ERK1/2, p38, TAK-1, PKC, FAK, and P3IK. Signals transmitted via these pathways change the activities of transcription factors such as Smad, AP-1, and NF-kB. This in turn causes changes in gene transcription and ultimately alters the whole cell's behavior and morphology. The cell begins the production collagen type I, TIMP-1, and alphaSMA. Activated HSCs can sustain their own activation by producing growth factors such as PDGF and TGF-beta. Despite the vast knowledge about the mechanisms causing liver fibrosis and cirrhosis, there is still no effective cure. Further studies are therefore needed to solve this problem.
Plewka
Krzysztof
K
Zakład Wirusologii i Immunologii, Instytut Mikrobiologii i Biotechnologii, UMCS w Lublinie, Lublin. hurin22@wp.pl
Szuster-Ciesielska
Agnieszka
A
Kandefer-Szerszeń
Martyna
M
D002630:Chemotactic Factors / Q000378:metabolism; D005109:Extracellular Matrix; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000473:pathology*; D008104:Liver Cirrhosis, Alcoholic / Q000473:pathology* / Q000503:physiopathology*; D015398:Signal Transduction
D002630:Chemotactic Factors; D006133:Growth Substances