Chitinase-3-like Protein 1: A Progranulin Downstream Molecule and Potential Biomarker for Gaucher Disease

EBioMedicine. 2018 Feb:28:251-260. doi: 10.1016/j.ebiom.2018.01.022. Epub 2018 Jan 31.


We recently reported that progranulin (PGRN) is a novel regulator of glucocerebrosidase and its deficiency associates with Gaucher Diseases (GD) (Jian et al., 2016a; Jian et al., 2018). To isolate the relevant downstream molecules, we performed a whole genome microarray and mass spectrometry analysis, which led to the isolation of Chitinase-3-like-1 (CHI3L1) as one of the up-regulated genes in PGRN null mice. Elevated levels of CHI3L1 were confirmed by immunoblotting and immunohistochemistry. In contrast, treatment with recombinant Pcgin, a derivative of PGRN, as well as imigluerase, significantly reduced the expressions of CHI3L1 in both PGRN null GD model and the fibroblasts from GD patients. Serum levels of CHIT1, a clinical biomarker for GD, were significantly higher in GD patients than healthy controls (51.16±2.824ng/ml vs 35.07±2.099ng/ml, p<0.001). Similar to CHIT1, serum CHI3L1 was also significantly increased in GD patients compared with healthy controls (1736±152.1pg/ml vs 684.7±68.20pg/ml, p<0.001). Whereas the PGRN level is significantly reduced in GD patients as compared to the healthy control (91.56±3.986ng/ml vs 150.6±4.501, p<0.001). Collectively, these results indicate that CHI3L1 may be a previously unrecognized biomarker for diagnosing GD and for evaluating the therapeutic effects of new GD drug(s).

Keywords: Chitinase-3-like-1; Gaucher disease; Lysosomal storage diseases; Progranulin.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Chitinase-3-Like Protein 1 / blood
  • Chitinase-3-Like Protein 1 / metabolism*
  • Chitinases / blood
  • Disease Models, Animal
  • Gaucher Disease / blood
  • Gaucher Disease / metabolism*
  • Granulins
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Progranulins
  • Up-Regulation


  • Biomarkers
  • Chitinase-3-Like Protein 1
  • GRN protein, human
  • Granulins
  • Grn protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • Chitinases