Abstract
Hepatic pathological angiogenesis (HPA) is the key event of hepatic fibrosis (HF). Xueshisanjia powder (XSSJS), a Chinese herbal compound, is beneficial for alleviating pathological angiogenesis of hepatic tissue. The present study attempts to reveal the effect and mechanism of XSSJS via regulating miR-29b-3p/VEGFA axis against pathological angiogenesis in HF. In in vitro model, human embryonic kidney 293T cells were transfected with miR-29b-3p mimics, whereby the expression of miR-29b-3p was tested by real-time quantitative polymerase chain reaction (RT-qPCR), ensued by Luciferase assay determining the relationship between miR-29b-3p and vascular endothelial cell growth factor A (VEGFA). In addition, miR-29b-3p mimic transfected into the activated hepatic stellate cell T6 (HSC-T6). The Cell-Counting-Kit 8 (CCK8) and 5-Bromodeoxyuridine (BrdU) staining were first utilized to detect the antiproliferative efficiency of XSSJS following the XSSJS compound serum intervention, and then used to observe the expression of transforming growth factor-β (TGF-β), VEGFA, platelet-derived growth factor (PDGF) via RT-PCR, Western blot (WB), and Immunofluorescence (IF) methods. During the in vivo model, XSSJS with boil-free granules were fed to Wistar rats with liver fibrosis caused by intraperitoneal injection of pig serum followed by the transfection of miR-29b-3p adeno-associated virus (AAV). Hematoxylin–Eosin (HE) staining was used for histopathology assessment. The expression of miR-29b-3p, VEGFA, PDGF, TGF-β have been investigated in liver tissue using RT-PCR, WB, IF. The results verified that XSSJS could up-regulate miR-29b-3p and suppress the expression of VEGFA, PDGA, and TGF-β. In mechanism, miR-29b-3p primarily targeted the 3′UTR of VEGFA. In conclusion, XSSJS could modulate miR-29b-3p/VEGFA axis to inhibit the pathological angiogenesis of HF.
Highlights
Hepatic fibrosis (HF) is a common pathological hallmark of chronic liver diseases (CLDs) [1]
Effect of XSSJS on the expression of miR29b-3p, vascular endothelial growth factor (VEGFA), transforming growth factor-β (TGF-β), platelet-derived growth factor (PDGF) in HF rats In quest for further proof of miR-29b-3p/VEGFA axis being involved in XSSJS-mediated PA alleviation in vivo, we investigated the effectiveness of XSSJS intervention on the expression of miR-29b-3p and VEGFA in liver fibrosis rats
We found that the expression of VEGFA, PDGF, TGF-β remained relatively low in normal liver tissues, and VEGFA, PDGF, TGF-β were significantly up-regulated in HF rats
Summary
Hepatic fibrosis (HF) is a common pathological hallmark of chronic liver diseases (CLDs) [1]. Hepatic pathological angiogenesis (HPA) associates strong implication in the development of HF, which is recognized as a central event in hepatic stellate cells (HSCs) activation [2,3], inflammatory response [4,5,6] and hepatic vascular resistance (IHVR) [7,8]. In the progression of HPA, vascular endothelial growth factor (VEGFA) contributes to the proliferation, migration, differentiation of vascular endothelial cells and the formation of vascular lumen [9,10,11], which eventually leads to intrahepatic angiogenesis and hepatic sinusoidal capillarization [12,13]. It is of great significance to restrain pathological angiogenesis for liver disease deterioration, especially targeting the excessive VEGF [14,15]. Accumulated evidence have demonstrated that the use of traditional Chinese medicines (TCMs)
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