Chitinase-3 like-protein-1 function and its role in diseases

Abstract

Non-enzymatic chitinase-3 like-protein-1 (CHI3L1) belongs to glycoside hydrolase family 18. It binds to chitin, heparin, and hyaluronic acid, and is regulated by extracellular matrix changes, cytokines, growth factors, drugs, and stress. CHI3L1 is synthesized and secreted by a multitude of cells including macrophages, neutrophils, synoviocytes, chondrocytes, fibroblast-like cells, smooth muscle cells, and tumor cells. It plays a major role in tissue injury, inflammation, tissue repair, and remodeling responses. CHI3L1 has been strongly associated with diseases including asthma, arthritis, sepsis, diabetes, liver fibrosis, and coronary artery disease. Moreover, following its initial identification in the culture supernatant of the MG63 osteosarcoma cell line, CHI3L1 has been shown to be overexpressed in a wealth of both human cancers and animal tumor models. To date, interleukin-13 receptor subunit alpha-2, transmembrane protein 219, galectin-3, chemo-attractant receptor-homologous 2, and CD44 have been identified as CHI3L1 receptors. CHI3L1 signaling plays a critical role in cancer cell growth, proliferation, invasion, metastasis, angiogenesis, activation of tumor-associated macrophages, and Th2 polarization of CD4+ T cells. Interestingly, CHI3L1-based targeted therapy has been increasingly applied to the treatment of tumors including glioma and colon cancer as well as rheumatoid arthritis. This review summarizes the potential roles and mechanisms of CHI3L1 in oncogenesis and disease pathogenesis, then posits investigational strategies for targeted therapies.

Role of Chitinase 3-Like 1 Protein in the Pathogenesis of Hepatic Insulin Resistance in Nonalcoholic Fatty Liver Disease

“…The WT C57BL/6 develop NAFLD/NASH like pathology on HFD in association with enhanced Chi3L1 gene expression levels which allowed us to access the role of this gene in the pathogenesis of insulin resistance. It will be important to examine the role of stellate cells that also have upregulated Chi3L1 protein expression on hepatocyte injury, insulin resistance and fibrosis as described [41,42].…”

“…The Chi3L1 gene is also involved in mediating inflammation, tissue remodeling, fat accumulation and cancer [12,[19][20][21]42]. Moreover, investigations have suggested that Chi3L1 serum levels correlate with tissue injury and the degree of hepatic fibrosis [52].…”

Key biomarkers within the colorectal cancer related inflammatory microenvironment

“…Thus, CHI3L1 binding to CD44v3 induces the activation of Erk, Akt, and β-catenin signaling pathways enhancing cancer metastasis 22 . In cell lines, CHI3L1 stimulation results in the phosphorylation of Erk1/2 23 and a recombinant CHI3L1 was reported to significantly enhance the proliferation of SW480 cells, through the activation of MAPK/Erk signaling pathway 24 . Overall, CHI3L1-induced MMP2 overexpression plays a crucial role in ECM regulation promoting cancer cell growth, proliferation, invasion, and metastasis 24 .…”

Key Biomarkers Within the Colorectal Cancer Related Inflammatory Microenvironment

“…Thus, CHI3L1 binding to CD44v3 induced the activation of Erk, Akt, and β-catenin signaling pathway enhancing cancer metastasis 23 . In cell lines, CHI3L1 stimulation results in the phosphorylation of Erk1/2 24 and a recombinant CHI3L1 was reported to signi cantly enhance the proliferation of SW480 cells, through the activation of MAPK/Erk signaling pathway 25 . Overall, CHI3L1-induced MMP2 overexpressionplays a crucial role in ECM regulation promoting cancer cell growth, proliferation, invasion, and metastasis 25 .…”