Myeloid KIF13B suppresses the STT3A/CTSD/THBS1 Axis to prevent MASH - PubMed
4 hours ago
- #macrophage-hepatocyte crosstalk
- #KIF13B
- #MASLD
- Myeloid KIF13B plays a crucial role in preventing Metabolic dysfunction-associated steatotic liver disease (MASLD).
- KIF13B expression is downregulated in monocyte-derived macrophages under MASLD conditions.
- Deletion of myeloid-derived Kif13b makes mice more susceptible to diet-induced MASLD.
- Kif13b deficiency impairs proteasome-dependent degradation of glycosyltransferase STT3A in macrophages.
- This leads to enhanced cathepsin D (CTSD) glycosylation and secretion, promoting liver lipid accumulation and inflammation.
- CTSD's harmful effects depend on its interaction with hepatocyte membrane protein Thrombospondin 1 (THBS1).
- The transcription factor ZNF384 is identified as an upstream regulator of KIF13B, binding directly to its promoter for activation.
- ZNF384 expression is also downregulated in MASLD.
- The study reveals a novel regulatory axis: ZNF384/KIF13B/STT3A/CTSD/THBS1, important for macrophage-hepatocyte crosstalk in MASLD progression.
- This axis provides potential therapeutic targets for MASLD treatment.