Table 4.
Role of miRNAs in cholangiocyte homeostasis and in cholangiopathies.
| Cohort | miRNA | Direction of effecta |
Affected mRNA |
Outcome of miRNA changes |
|---|---|---|---|---|
| Healthy | miR-33a | – | ABCA1, ABCG1 | Maintains cellular cholesterol efflux |
| – | ABCB11 | Maintains homeostatic BSEP expression for bile acid export into bile canaliculi | ||
| – | ATP8B1 | Maintains membrane polarity and secretory function | ||
| miR-144 | – | ABCA1 | Maintains plasma HDL levels | |
| miR-122, miR-422a | – | CYP7A1 | Maintains homeostatic bile acid synthesis | |
| miR-98, let-7 | – | CIS | Suppression of CIS may indirectly suppress NF-κβ | |
| miR-513 | – | B7-H1 | Decrease in IFN-γ induced B7-H1 expression (which has dual functions in T cell regulation) | |
| Experimental bliary obstruction (BDL mice) | miR-21 | Upregulated | Smad-7 | Bile duct proliferation and fibrosis |
| Experimental sclerosing cholangitis (Mdr2−/− mice) | miR-24 | Downregulated | MEN1 | Limits expression of fibrosis |
| Experimental sclerosing cholangitis (BDL and DDC fed mice) | miR-7-a-1, miR-7-a-2 | Upregulated | Ngn-3 | Inhibits promitotic effect of Ngn-3, thus decreasing cholangiocyte proliferation and collagen deposition |
| PBC | miR-506 | Upregulated | AE2 | Decreased AE2 expression leads to impaired biliary secretion |
| Biliary atresia | miR-200b | Upregulated | FOG2 | Increased PI3K/AKT signalling, leading to HSC cell growth and migration with increased fibrosis |
| miR-21 | Upregulated | PTEN | Increased AKT signalling, leading to HSC cell growth and migration with increased fibrosis | |
| PCK rat | miR-15a | Downregulated | Cdc25A | Cell cycle progression and cyst expansion in normal rat cholangiocytes |
Abbreviations: AE2, anion exchanger2; BDL, bile-duct ligation; BSEP, bile salt exporter protein; Cdc25A, cell division cycle 25A; CIS, cytokine-inducible Src homology 2-containing protein; DDC, 3,5;diethoxycabonyl-1,4-dihydrocollidine; FOG2, friend of GATA 2; HDL, high density lipoprotein; IFN, interferon; NF-κβ; nuclear factor kappa-light-chain enhancer of activated B cells; Ngn-3, neurogenin-3; PBC, primary biliary cholangitis; PCK, polycystic rat; PI3K, phosphoinositide 3-kinase; PSC, primary sclerosing cholangitis; PTEN, phosphatase and tensin homolog; Smad; small mothers against decapentaplegic.
No direction of effect is listed for miRNA described in homeostatic circumstances (e.g., “healthy”) as the listed direction of effect is relative to controls. miRNAs are inherently inhibitory; that is, they inhibit their target mRNAs.