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Fig. 4
Cellular expression of IL-6R and gp130. Most IL-6R expressing cells such as hepatocytes express far
more gp130 molecules on the cell surface than IL-6R. These cells are responsive to IL-6 but become far more
responsive to the complex of IL-6 and sIL-6R
The role of gp130 signaling is also most important in adult
stem cell physiology. Muscle satellite cells are activated upon tissue
injury. The proliferative response of satellite cells upon injury is
dependent on IL-6 and STAT3 activation (
85
). The significance of
mesenchymal stem cells is becoming apparent as a therapeutic plat-
form (
86
). Upon integration into damaged tissue, these cells dif-
ferentiate and function as parenchymal cells. We have shown that
IL-6 trans-signaling is essential for the hepatic differentiation of
mesenchymal stem cells in the damaged liver (
87
). Hyper-IL-6
through trans-signaling is important for neurogenesis and gliogen-
esis of neuronal stem cells, through MAPK/CREB and STAT3,
respectively (
30
). Oval cells are liver progenitors. In IL-6 knockout
mice, oval cell population is significantly reduced. IL-6 trans-signaling
induces an enhanced STAT3 activation signal leading to an increased
proliferation of oval cells (
88
). In the hematopoietic system, IL-6
trans-signaling supports the maintenance and proliferation of
hematopoietic stem cells (
32, 80, 89, 90
).
7
The Role of the IL6-gp130 in Tissue Protection
In addition to its role in tissue regeneration, the IL-6-gp130 path-
way was shown to be important for the protection from tissue
injury. Interestingly, the
-cells in the pancreas express functional
IL-6R. IL-6 is essential to preserve the
α
-cell mass under a high-fat
diet stress (
91
). The importance of IL-6 in liver protection was
shown in numerous examples in which the liver was under stress.
The plasma level of IL-6 in acute and chronic liver injury is
increased, possibly serving to signal through IL-6-gp130 to coor-
dinate protective measures (
92-94
). In an acute inflammation
model of bile duct ligation, the signaling through IL-6-gp130 is
essential to protect from liver failure (
95
). Signaling through
IL-6-gp130 protects from CCl
4
-mediated liver injury (
93
) as well
α
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