THY1 - Thy-1 cell surface antigen |Elisa - Clia - Antibody - Protein

Background

THY1, also known as CD90, is a glycoprotein encoded by the THY1 gene in humans. Initially identified as a marker for T cells, THY1 is now known to have broader expression across a variety of cell types, including neurons, fibroblasts, endothelial cells, and certain stem cells. THY1 plays a significant role in cell-cell and cell-matrix interactions and has been extensively studied in relation to immune regulation, inflammation, fibrosis, tissue regeneration, and neurobiology. Due to its multifunctional role, THY1 is a notable target in therapeutic research, especially in fields related to fibrosis and regenerative medicine.

In humans, THY1 is located on chromosome 11q23.3 and consists of a single-copy gene with limited allelic variation. THY1 is widely conserved across vertebrates, indicating its importance in basic cellular functions. The expression of THY1 varies depending on tissue type and developmental stage, with its role in signal transduction and regulation of immune responses contributing to tissue maintenance, repair, and homeostasis.

Protein Structure

THY1 is a type I transmembrane protein with a distinct structure suited for its interactions with other cellular molecules.

Extracellular Domain:

• The extracellular domain of THY1 is relatively small and comprises a single immunoglobulin-like (Ig-like) domain of the variable (V)-type. This Ig-like domain is essential for mediating interactions with various ligands, including integrins and other cell surface receptors.
• THY1 is heavily glycosylated with N-linked carbohydrate side chains that contribute to its function, stability, and structural integrity. Glycosylation also aids in the recognition and interaction of THY1 with extracellular matrix components and other cell adhesion molecules.
• THY1 attaches to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor instead of a traditional transmembrane domain. This GPI anchor is linked to the C-terminal end of the protein, which allows THY1 to exist in lipid rafts within the cell membrane. Lipid rafts are microdomains rich in cholesterol and sphingolipids, facilitating efficient signal transduction and protein interactions.

Functional Domains:

• Although THY1 has a simple structure compared to multi-domain receptors, its Ig-like domain and GPI anchor enable it to perform various complex functions. The GPI anchor, in particular, facilitates lateral mobility within the cell membrane, allowing THY1 to quickly recruit signaling molecules and interact with other cell surface receptors.
• Due to the lack of a cytoplasmic domain, THY1 relies on interactions with cytoplasmic signaling molecules in nearby cells or within the lipid raft microdomains for downstream signaling.

Classification and Subtypes

THY1 (CD90) belongs to the immunoglobulin superfamily and is classified as a single-chain cell adhesion molecule. Unlike some other cell adhesion molecules, THY1 has no known subtypes; however, its expression varies across cell types and species. In humans, THY1 has distinct glycosylation patterns depending on cell type, which can subtly influence its functional characteristics. Additionally, the THY1 protein can undergo alternative splicing in some organisms, though this has not been extensively characterized in humans.

Function and Biological Significance

THY1 is multifunctional, primarily associated with cell adhesion, immune modulation, and signal transduction. The functions of THY1 are mediated through its interactions with other cell surface receptors, integrins, and extracellular matrix components.

Cell Adhesion and Migration:

• THY1 interacts with integrins, particularly αvβ3 integrins on fibroblasts and endothelial cells, which is crucial for mediating cell adhesion, migration, and tissue remodeling.
• THY1-integrin interactions facilitate the migration of fibroblasts and immune cells to sites of injury or inflammation, thus promoting wound healing and tissue repair.
• It also plays a role in neuron-neuron adhesion, particularly in the central nervous system (CNS), where it helps in neuron outgrowth, synapse formation, and axonal guidance, contributing to neurodevelopment and neural regeneration.

Regulation of Inflammation and Immune Response:

• THY1 acts as a modulator of immune cell activation and migration. It can bind to integrins on T cells and neutrophils, playing a role in T cell activation and neutrophil adhesion, processes essential for immune surveillance and inflammation control.
• Through these interactions, THY1 influences both pro-inflammatory and anti-inflammatory responses, depending on the cellular context, and contributes to immune cell recruitment during infection or tissue injury.

Role in Fibrosis:

• THY1 is actively involved in fibrotic processes, where it has been shown to regulate fibroblast activation. In the liver, lungs, and kidneys, THY1 expression is modulated during fibrosis, a condition characterized by excessive deposition of extracellular matrix.
• Studies have demonstrated that THY1 is a marker for fibroblast subsets that either promote or inhibit fibrosis, and the absence of THY1 on fibroblasts can lead to increased fibrosis, indicating its protective role in some contexts.
• THY1 signaling affects fibroblast differentiation and activation, contributing to the modulation of fibrotic pathways, particularly in diseases like idiopathic pulmonary fibrosis (IPF).

Stem Cell Marker:

• THY1 is commonly used as a marker for mesenchymal stem cells (MSCs) and other progenitor cells, particularly in bone marrow and adipose tissues. THY1-positive MSCs are known for their capacity to differentiate into various cell types, including adipocytes, chondrocytes, and osteocytes.
• In stem cell biology, THY1-positive cells are identified for use in regenerative medicine, where they are employed in tissue repair and wound healing therapies.

Neuroprotective and Regenerative Functions:

• In the nervous system, THY1 expression is associated with neuroprotective functions. THY1 has been implicated in neuronal differentiation, neuroprotection, and regeneration following injury.
• THY1’s role in axonal regeneration and neurite outgrowth makes it significant in studying and potentially treating neurodegenerative diseases and brain injuries.

Clinical Issues

Fibrosis:

• THY1 expression is altered in several fibrotic diseases, including pulmonary, hepatic, and renal fibrosis. In pulmonary fibrosis, loss of THY1 expression in fibroblasts has been linked to increased myofibroblast activity, excessive collagen deposition, and lung tissue stiffening, which worsen the disease.
• Targeting THY1 signaling in fibrosis holds therapeutic potential, as enhancing THY1 expression in certain fibroblast populations could reduce fibrotic activity.

Cancer:

• THY1 has a complex role in cancer. In some cancers, such as glioblastoma, THY1 expression is associated with tumor cell adhesion and migration, which facilitates metastasis. In contrast, in other cancers, THY1 acts as a tumor suppressor, as seen in melanoma, where THY1 expression inhibits cell proliferation.
• Targeting THY1 expression and its interaction with integrins has been explored as a therapeutic strategy to limit cancer cell migration and metastasis, especially in tumors where THY1 contributes to invasive behavior.

Neurodegenerative Diseases:

• Due to its involvement in neuroprotective and regenerative processes, THY1 is being studied as a potential therapeutic target in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. Enhancing THY1 expression may support neuronal health and counteract degenerative processes.
• In multiple sclerosis, THY1 is also being investigated for its role in T-cell-mediated neuroinflammation and potential to modulate immune responses within the CNS.

Stem Cell and Regenerative Medicine:

• THY1 is a key marker for isolating mesenchymal stem cells for use in regenerative medicine, particularly in cartilage, bone, and adipose tissue repair. THY1-positive stem cells have shown promise in clinical applications for musculoskeletal injuries, osteoarthritis, and cardiac repair.

Summary

THY1 (CD90) is a multifunctional cell surface glycoprotein that plays critical roles in cell adhesion, immune modulation, and tissue regeneration. Structurally, it is a type I transmembrane protein anchored to the cell membrane via a GPI anchor, featuring a single Ig-like domain that enables interactions with various cellular receptors and extracellular matrix components. THY1’s versatile functions include promoting cell migration, mediating immune responses, and regulating fibroblast activation, making it essential in inflammation, fibrosis, stem cell biology, and neurobiology.

THY1 has clinical relevance across various fields, including fibrotic diseases, cancer, neurodegenerative diseases, and regenerative medicine. Its dual role in tumor suppression and facilitation of metastasis, depending on the cancer type, highlights the complexity of THY1 function. In fibrotic diseases, THY1 acts as a protective factor by inhibiting excessive fibroblast activity, whereas in the CNS, it contributes to neuronal protection and regeneration.