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. 2018 Sep 28;7:F1000 Faculty Rev-1571. [Version 1] doi: 10.12688/f1000research.15695.1

Figure 1. Role and regulation of host microRNAs in hepatic schistosomiasis.

Figure 1.

( A) Transforming growth factor-beta 1 (TGF-β1) and interleukin-13 (IL-13) are the primary cytokines responsible for fibrosis induced by schistosome infection by activation of SMAD pathway. In hepatic stellate cells, miR-21, induced by TGF-β1 and IL-13, prompted TGF-β1/SMAD and IL-13/SMAD signaling to induce fibrogenic effects by relieving the inhibitory effect of SMAD7 in the SMAD pathway. MiR-351 was negatively regulated by interferon-gamma (IFN-γ) via activation of the STAT1 pathway and promoted fibrogenesis by targeting vitamin D receptor (VDR), a newly identified negative regulator of the SMAD pathway. Moreover, infection-induced downregulation of miR-203 expression resulted in hepatic fibrosis by relieving the inhibition of IL-33, which elevated the expression of IL-13. ( B) In hepatic macrophages, various T helper 2 (Th2) cytokines, such as IL-4, IL-13, and IL-10, promoted the transcription of miR-146b by activating STAT3/6, and elevated miR-146b inhibited the IFN-γ–induced differentiation of macrophages into M1 cells by targeting STAT1. iNOS, inducible nitric oxide synthase.