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. Author manuscript; available in PMC: 2019 Jan 5.
Published in final edited form as: Lab Invest. 2018 Jul 5;98(11):1449–1464. doi: 10.1038/s41374-018-0093-9

Figure 7.

Figure 7

In the Mdr2−/− mouse model, there is activation of the Sct/SR axis that increases microRNA 125b-dependent TGF-β1 biliary secretion that: (i) increases cholangiocyte senescence by an autocrine mechanism; and (ii) triggers liver fibrosis by a paracrine loop. The increase in TGF-β1 biliary secretion (mediated by the Sct/SR/microRNA 125b axis) leads to enhanced VEGF-A expression, which subsequently increases cholangiocyte senescence (by an autocrine loop) and increases fibrogenic activity but decreases cellular senescence of HSCs by a paracrine loop.