Coordinated signaling of activating transcription factor 6α and inositol-requiring enzyme 1α regulates hepatic stellate cell-mediated fibrogenesis in mice
Fei Xue, Jianwen Lu, Samuel C. Buchl, Liankang Sun, Vijay H. Shah, Harmeet Malhi, Jessica L. Maiers
2021American Journal of Physiology-Gastrointestinal and Liver Physiology15 citationsDOIOpen Access PDF
Abstract
ATF6α is a critical driver of hepatic stellate cell (HSC) activation in vitro. HSC-specific deletion of Atf6a limits fibrogenesis in vivo despite increased IRE1α signaling. Conditional deletion of Ire1α from HSCs limits fibrogenic gene transcription without impacting overall fibrosis. This could be due in part to observed upregulation of the ATF6α pathway. Dual loss of Atf6a and Ire1a from HSCs worsens fibrosis in vivo through enhanced HSC activation.
Topics & Concepts
Hepatic stellate cellDownregulation and upregulationTranscription factorCell biologyIn vivoHepatic fibrosisSignal transductionFibrosisBiologyCancer researchChemistryGeneInternal medicineMedicineEndocrinologyBiochemistryGeneticsLiver physiology and pathologyLiver Disease Diagnosis and TreatmentEndoplasmic Reticulum Stress and Disease