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

Abstract

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).

• Authors: Jinlong Jian, Yuehong Chen, Rossella Liberti, Wenyu Fu, Wenhuo Hu, Rachel Saunders-Pullman, Gregory M Pastores, Ying Chen, Ying Sun, Gregory A Grabowski, Chuan-Ju Liu
• Journal: EBioMedicine (EBioMedicine) Vol. 28 Pg. 251-260 (Feb 2018) ISSN: 2352-3964 [Electronic] Netherlands
• PMID: 29396296 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

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

Topics

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