Authors: Shalil Khanal, Yuanhang Liu, Adebowale O. Bamidele, Alexander Q. Wixom, Alexander M. Washington, Nidhi Jalan-Sakrikar, Shawna A. Cooper, Ivan Vuckovic, Song Zhang, Jun Zhong, Kenneth L. Johnson, M. Cristine Charlesworth, Iljung Kim, Yubin Yeon, Sangwoong Yoon, Yung-Kyun Noh, Chady Meroueh, Abdul Aziz Timbilla, Usman Yaqoob, Jinhang Gao, Yohan Kim, Fabrice Lucien, Robert C. Huebert, Nissim Hay, Michael Simons, Vijay H. Shah, Enis Kostallari
Published: 2024-06-28
Source: Full article
Liver fibrosis is characterized by the activation of perivascular hepatic stellate cells (HSCs), the release of fibrogenic nanosized extracellular vesicles (EVs), and increased HSC glycolysis. Nevertheless, how glycolysis in HSCs coordinates fibrosis amplification through tissue zone-specific pathways remains elusive. Here, we demonstrate that HSC-specific genetic inhibition of glycolysis reduced liver fibrosis. Moreover, spatial transcriptomics revealed a fibrosis-mediated up-regulation of EV-related pathways in the liver pericentral zone, which was abrogated by glycolysis genetic inhibition. Mechanistically, glycolysis in HSCs up-regulated the expression of EV-related genes such as Ras-related protein Rab-31 (