Table 1.
Autocrine factors secreted by cholangiocytes and their role in proliferation or fibrogenesis
| Autocrine Factor | Mechanism/Outcome | ↑/↓ | References | |
|---|---|---|---|---|
| Proliferation | Secretin | cAMP | ↑ | 1, 5, 6, 30, 41 |
| Glucagon-like peptide | cAMP, Ca2+, PI3K | ↑ | 70 | |
| Leptin | JAK/STAT/ERK1/2 | ↑ | 25 | |
| Insulin-like growth factor 1 | PI3K | ↑ | 10, 34 | |
| Progesterone | Ca2+/PKC | ↑ | 38 | |
| Prolactin | cAMP, JAK/STAT, PKC, Src | ↑ | 102 | |
| Follicle-stimulating hormone | cAMP, PKC | ↑ | 68 | |
| Testosterone | cAMP | ↑ | 111 | |
| Serotonin | Inhibits proliferation through IP3 | ↓ | 72 | |
| Met-enkephalin | Inhibits proliferation through IP3 | ↓ | 71 | |
| Nerve growth factor | PI3K, ERK1/2 | ↑ | 37, 110 | |
| CGRP | cAMP | ↑ | 42 | |
| VEGF | PKC, ERK 1/2 | ↑ | 26, 36, 69, 96 | |
| Fibrogenesis | Renin-angiotensin | TGF-β1, NADPH oxidase, TNF-α, procollagen | 14, 51, 77, 88, 112 | |
| Platelet-derived growth factor | EMT, stellate cell activation | 45, 56 | ||
| Transforming growth factor-β | αVβ6 integrin, collagen, laminin, fibronectin, others | 66, 75, 87, 99, 101 | ||
| αVβ6 integrin | TGF-β1, collagen, fibronectin | 87, 100 | ||
| Connective tissue growth factor | TGF-β1, collagen, activates fibroblasts | 20, 92 | ||
| Endothelin 1 | collagen, apoptosis, decreases VEGF | 26, 66 | ||
| Hedgehog | osteopontin, cxcl16, EMT, activates MF-HSCs | 82–86 | ||
| Substance P | collagen, α-SMA | 40 | ||
CGRP, calcitonin gene-regulated peptide; VEGF, vascular endothelial growth factor; PI3K, phosphoinositide 3-kinase; IP3, inositol 1,4,5-trisphosphate; EMT, epithelial-mesenchymal transition; MF-HSCs, myofibroblast-hepatic progenitor cells; SMA, smooth muscle actin.