Hepatocyte TLR4 triggers inter-hepatocyte Jagged1/Notch signaling to determine NASH-induced fibrosis
Junjie Yu, Changyu Zhu, Xiaobo Wang, KyeongJin Kim, Alberto Bartolomé, Paola Dongiovanni, Katherine P. Yates, Luca Valenti, Michele Carrer, Thorsten Sadowski, Li Qiang, Ira Tabas, Joel E. Lavine, Utpal B. Pajvani
Abstract
-acetylgalactosamine (GalNAc)-modified siRNA, both of which reduced NASH diet-induced liver fibrosis in mice. Overall, these data demonstrate that increased hepatocyte Jagged1 is the proximal hit for Notch-induced liver fibrosis in mice and suggest translational potential of Jagged1 inhibitors in patients with NASH.
Topics & Concepts
HepatocyteFibrosisTLR4Liver fibrosisCell biologyHepatocyte growth factorSignal transductionChemistryCancer researchMedicineBiologyInternal medicineBiochemistryReceptorIn vitroPediatric Hepatobiliary Diseases and TreatmentsLiver physiology and pathologyLiver Disease Diagnosis and Treatment