CD36-PPARγ-SPP1 axis mediates hepatocyte-macrophage coordination to drive MASLD-related liver fibrosis - PubMed
2 days ago
- #Liver Fibrosis
- #CD36
- #MASLD
- The study identifies the CD36-PPARγ-SPP1 axis as a key mechanism in MASLD-related liver fibrosis.
- CD36+ macrophages (LAMs) expand in MASLD livers and correlate with fibrosis severity.
- Macrophage-specific CD36 deletion reduces steatosis, liver enzymes (ALT, AST), and fibrosis in mouse models.
- CD36 mediates lipid transfer from hepatocytes to LAMs, activating PPARγ which stimulates SPP1 secretion.
- SPP1 activates hepatic stellate cells, contributing to fibrosis.
- The CD36-PPARγ-SPP1 gene signature is linked to fibrosis and steatosis in patients.
- Pharmacological CD36 inhibition reduces lipid uptake and SPP1 release, attenuating fibrosis.
- Combination therapy targeting CD36 and PPARγ shows synergistic antifibrotic effects.