Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 19 4 2020 08 25 397 408 Wei Zhan Department of Colorectal Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, China Xin Liao Department of Imaging, Affiliated Hospital of Guizhou Medical University, Guiyang, China Zhongsheng Chen Guizhou Medical University, Guiyang, China Lianghe Li Guizhou Medical University, Guiyang, China Tian Tian Guizhou Medical University, Guiyang, China AND Department of Pathology, Guiyang Maternal and Child Health Hospital, Guiyang, China Rui Li Department of Traditional Chinese Medicine, Guizhou Provincial People’s Hospital, Guiyang, China 2019 06 24 2020 03 10 To detect the leucine-rich repeats and immunoglobulin 1 (LRIG1) ameliorated liver fibrosis and hepatic stellate cell (HSC) activation via inhibiting sphingosine kinase 1 (SphK1)/Sphingosine-1-Phosphate (S1P) pathway. C57BL/6 male mice (eight weeks old) were intraperitoneal injection with 10% carbon tetrachloride (CCl4) as an in vivo model. The LX-2 cells were induced as amodel for in vitro study by TGF-β (10 ng/mL). The Hematoxylin-eosin (HE) staining, Masson staining, and Sirius red staining results showed that CCl4 caused serious fibrosis and injury in liver tissue, high expression of type I collagen α1 chain (Col1α1) and α-smooth muscle actin (α-SMA) in liver tissue, while the LRIG1 expression level was significantly decreased in LX-2 cell lines. The LRIG1 ameliorated CCl4-induced liver fibrosis, indicated by the fibronectin, α-SMA, LRIG1, SphK1, Col1α1, fibrin Connexin 1 (Fn1), tissue inhibitor of metalloproteinase-1 (TIMP1), sphingosine-1-phosphate (S1P), transforming growth factor-beta 1 (TGF-β1) expression level changes. Similar results were observed in TGF-β1 treated of LX-2 cells. However, the effects were attenuated by treatment with LRIG1. Moreover, SphK1 inhibitors abrogated the effect of LRIG1 on fibrosis. These results demonstrated that LRIG1 improved liver fibrosis in vitro and in vivo via suppressing the SphK1/S1P pathway, indicating its potential use in the treatment of liver fibrosis. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2443