Clusterin is protective for liver fibrosis through mesothelial-specific LRP2 receptor mediated endocytosis

During liver fibosis, the CLU protein was overexpressed of hepatocytes. Loss of function perform showed that CLU is protective for liver fibrosis. Mechanismly, we found LRP2 postive cells were increased after hrCLU administration in fibrotic CLUKO mice. Then single cell analysis domenstrated that LRP2 positive cells were mesothelial cells, which play a critical role of endocytosis during fibrosis resolution. Taken together, we identify clusterin as a protective chaperone that can reverse liver fibrosis and clear extracellular matrix, which targets LRP2 signaling mediated endocytosis. Overall design: The liver cells of three CLUKO mice administrated human recombinant clusterin during CCL4 injection and WT mice treated with CCL4 injection for 0, 2, 4 weeks were pooled and loaded onto microwell chip using the Singleron Matrix® Single Cell Processing System. The scRNA-seq libraries were constructed according to the protocol of the GEXSCOPE® Single Cell RNA Library Kits (Singleron)