Blockade of the Notch1/Jagged1 pathway in Kupffer cells aggravates ischemia-reperfusion injury of orthotopic liver transplantation in mice.

Blockade of the Notch1/Jagged1 pathway in Kupffer cells aggravates ischemia-reperfusion injury of orthotopic liver transplantation in mice. Autoimmunity. 2019 Jul 19;:1-9 Authors: Bai H, Wen J, Gong JP, Wu H, Yuan FC, Cao D, Wu YK, Lai X, Wang MH Abstract Liver ischemia-reperfusion injury (IRI) represents a risk factor for early graft dysfunction and an obstacle to expanding donor pool in orthotopic liver transplantation (OLT). Kupffer cells (KCs) are the largest antigen-presenting cell (APC) group and the primary modulators of inflammation in liver tissues. The vital role of Notch1/Jagged1 pathway in mouse OLT model has been reported, however, its potential therapeutic mechanism is unknown. Here, we made use of short hairpin RNA-Jagged1 and AAV-Jagged1 to explore the effects of Notch1/Jagged1 pathway in OLT. In vitro, blockade of Notch1/Jagged1 pathway downregulated the expression of Hairy and enhancer of split-1 (Hes1) gene, which in turn increased the proinflammatory effects of KCs. Moreover, the anti-inflammatory effects of Notch1/Jagged1 pathway were induced by inhibiting Hes1/gene of phosphate and tension/protein kinase B/Toll-like receptor 4/nuclear factor kappa B (Hes1/PTEN/AKT/TLR4/NF-κB) axis in KCs. In vivo, we used a well-established mouse model of OLT to mimic clinical transplantation. Mice were stochastically divided into 6 groups: Sham group (n = 15); Normal saline (NS) group (n = 15); Adeno-associated virus-g...
Source: Autoimmunity - Category: Allergy & Immunology Tags: Autoimmunity Source Type: research