CHIA

What is CHIA protein?

CHIA (chitinase acidic) gene is a protein coding gene which situated on the short arm of chromosome 1 at locus 1p13. CHIA is an acidic mammalian chitinase belonging to the 18-glycosidase family. This enzyme is expressed in mammalian gastrointestinal epithelial cells and in certain immune cells, such as neutrophils and macrophages. CHIA expression is regulated by a variety of factors, including inflammation and infection. In addition, the expression of CHIA is also influenced by gene regulation. The study found that the expression pattern of CHIA gene is different in different mammals, which may reflect their evolution during adaptation to different ecological niches. The CHIA protein is consisted of 476 amino acids and its molecular mass is approximately 52.3 kDa.

What is the function of CHIA protein?

CHIA is expressed in the epithelial cells of the gastrointestinal tract and is involved in the degradation of chitin, which helps digest these substances by hydrolyzing the beta-1, 4-glucoside bonds in chitin. CHIA is expressed in certain immune cells, such as neutrophils and macrophages, and may be involved in host immune responses and defense mechanisms. CHIA can act as a pattern recognition receptor, recognizing chitin, a pathogen-associated molecular pattern (PAMP) that activates the host's immune response. It can degrade chitin in the cell wall of fungi, thus inhibiting the growth and spread of fungi. CHIA may play a role in tissue repair and remodeling, especially after inflammation and injury. The activity of CHIA may affect the composition of extracellular matrix and cell migration.

CHIA Related Signaling Pathway

CHIA is involved in multiple signaling pathways that are involved in processes such as immune response, extracellular matrix remodeling, cell migration, and inflammation regulation. In terms of immune response, CHIA can act as a pattern recognition receptor to recognize chitin, a pathogen-associated molecular pattern (PAMP), and thus activate host immune responses, including the release of inflammatory factors and activation of immune cells through Toll-like receptor (TLR) signaling and NF-κB signaling. In addition, the role of CHIA in the digestive system is also related to the signaling pathway, which is involved in the degradation of chitin in food and may affect the metabolic and immune status of the host by influencing the interaction between the gut microbiome and the host.

CHIA Related Diseases

CHIA is an enzyme that is expressed in the human body and has been linked to a variety of diseases. CHIA has been linked to genetic disorders such as asthma and Gaucher disease. In addition, mutations in the CHIA gene have also been associated with some metabolic diseases, migraines, congestive heart failure, and arterial failure. CHIA, through its role in digestion and absorption, as well as regulation of interleukin-13 expression, may play a role in the development and progression of these diseases.

Bioapplications of CHIA

In the field of agriculture and biological control, CHIA related research may contribute to the development of novel biopesticides to control pests and diseases by inhibiting chitin synthesis or degradation in pests and pathogens. In addition, the application of CHIA in medicine and disease treatment is also of concern, especially in respiratory diseases such as asthma, where CHIA is associated with inflammatory response and may be a potential target for the treatment of such diseases. In the study of gastric cancer, the expression level of CHIA is related to the occurrence and development of the disease, so it may be a new target for the treatment of gastric cancer.

Case Study 1: Dominik Hartl, 2009

Acidic mammalian chitinase (AMCase) is produced during and plays an important role in the pathogenesis of Th2-mediated diseases and antiparasite responses. However, the effector responses of AMCase in these settings have not been adequately defined and the relationship(s) between its chitinolytic and other biologic properties have not been investigated. In these studies, AMCase is demonstrate to protect airway epithelial cells from Fas ligand- and growth factor withdrawal-induced apoptosis. This cytoprotection was associated with Akt phosphorylation and abrogated when the PI3K/Akt pathway was inhibited. Comparable cytoprotection was also seen in experiments comparing wild-type AMCase and mutant AMCase that lacked chitinolytic activity. Importantly, the apoptosis-inhibiting effect of enzymatically active and inactive AMCase was abrogated by treatment with allosamidin. These studies demonstrate that secreted AMCase feeds back in an autocrine and/or paracrine manner to protect pulmonary epithelial cells from growth factor withdrawal- and Fas ligand-induced apoptosis.

Fig1. Intracellular AMCase was stained in permeabilized pan-Cytokeratin+ epithelial cells in wildtype (WT) and IL-13 transgenic overexpressing (IL-13 TG).

Fig2. Intracellular phosphorylated Akt was analyzed by flow cytometry in A549 cells transfected with the empty vector (Vector) or with full-length human AMCase.

Case Study 2: Yifan Wu, 2024

Ascariasis (roundworm) is the most common parasitic helminth infection globally and can lead to significant morbidity in children including chronic lung disease. Children become infected with Ascaris spp. via oral ingestion of eggs. It has long been assumed that Ascaris egg hatching and larval translocation across the gastrointestinal mucosa to initiate infection occurs in the small intestine. Here, this study shows that A. suum larvae hatched in the host stomach in a murine model. Larvae utilize acidic mammalian chitinase (AMCase; acid chitinase; Chia) from chief cells and acid pumped by parietal cells to emerge from eggs on the surface of gastric epithelium. Furthermore, antagonizing AMCase and gastric acid in the stomach decreases parasitic burden in the liver and lungs and attenuates lung disease. Given Ascaris eggs are chitin-coated, the gastric corpus would logically be the most likely organ for egg hatching, though this is the first study directly evincing the essential role of the host gastric corpus microenvironment.

Fig3. Ascaris eggs were treated with recombinant AMCase under acidic and neutral pH in vitro.

Fig4. Respiratory system resistance (RRS) was assessed after intravenous injection of increasing doses of acetylcholine (Ach) at 12 days post infection.

CHIA has several biochemical functions, for example, carbohydrate binding,chitin binding,chitinase activity. Some of the functions are cooperated with other proteins, some of the functions could acted by CHIA itself. We selected most functions CHIA had, and list some proteins which have the same functions with CHIA. You can find most of the proteins on our site.

CHIA has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with CHIA here. Most of them are supplied by our site. Hope this information will be useful for your research of CHIA.