TGFBI

What is TGFBI protein?

TGFBI gene (transforming growth factor beta induced) is a protein coding gene which situated on the long arm of chromosome 5 at locus 5q31. This gene encodes an RGD-containing protein that binds to type I, II and IV collagens. The RGD motif is found in many extracellular matrix proteins modulating cell adhesion and serves as a ligand recognition sequence for several integrins. This protein plays a role in cell-collagen interactions and may be involved in endochondrial bone formation in cartilage. The protein is induced by transforming growth factor-beta and acts to inhibit cell adhesion. The TGFBI protein is consisted of 683 amino acids and TGFBI molecular weight is approximately 74.7 kDa.

What is the function of TGFBI protein?

The TGFBI protein, also known as transforming growth factor-beta-induced protein, plays a multifaceted role in cellular processes. It is primarily involved in the regulation of cell adhesion, migration, and proliferation through its interactions with extracellular matrix components such as collagens and integrins. TGFBI is also implicated in wound healing, angiogenesis, and immune response modulation. Additionally, dysregulation or mutations in the TGFBI gene have been associated with various diseases, including corneal dystrophies and certain types of cancer, highlighting its importance in maintaining tissue homeostasis and disease pathogenesis.

Fig1. TGFBI as a tumor suppressor. (Armando Corona, 2021)

TGFBI related signaling pathway

TGFBI protein plays a significant role in cell adhesion, tumor progression, and response to chemotherapy. It is involved in the regulation of the Wnt signaling pathway and can act as both a tumor promoter and suppressor depending on the cancer type and stage. Elevated levels of TGFBI have been correlated with poorer clinical outcomes in various cancers, and it may also serve as a biomarker for chemotherapy resistance and tumor progression.

TGFBI related diseases

TGFBI is associated with several diseases primarily due to mutations or dysregulation of the TGFBI gene. The most notable conditions include corneal dystrophies such as granular and lattice corneal dystrophies, which affect the transparency and structure of the cornea leading to vision impairment. Additionally, aberrations in TGFBI have been linked to various cancers, including breast and lung cancer, where it can influence cell proliferation, migration, and invasion. Moreover, TGFBI has roles in fibrotic diseases and certain connective tissue disorders, underscoring its broad impact on tissue homeostasis and disease pathology.

Fig2. TGFBI as a tumor promoter. (Armando Corona, 2021)

Bioapplications of TGFBI

TGFBI, or transforming growth factor-beta-induced protein, is an extracellular matrix protein that plays a significant role in various cellular processes, including cell adhesion, proliferation, and migration. It has been implicated in tumor growth, angiogenesis, apoptosis, and metastasis in several types of cancer, such as colon, head and neck squamous, renal, and prostate. TGFBI also functions as a prominent marker in epithelial-mesenchymal transition (EMT) and is associated with lymph node metastasis. Moreover, it demonstrates immunosuppressive effects within the tumor immune microenvironment, making it a potential therapeutic target for cancer treatment.

Case Study 1: Seul Gi Lee, 2021

Studies indicate that extracellular matrix (ECM) remodeling and the microenvironment are closely linked to adipogenesis and adipose angiogenesis. This research shows that transforming growth factor-beta induced (TGFBI) inhibits angiogenesis triggered by adipocyte-conditioned medium (Ad-CM) both in vitro and in vivo. TGFBI knockout (KO) mice had more blood vessels in adipose tissue, with increased infiltration into Matrigel containing Ad-CM. TGFBI treatment reduced migration and tube formation in Ad-CM-stimulated SVEC-10 endothelial cells by suppressing the Src and ERK signaling pathways. Thus, TGFBI inhibits adipose angiogenesis by downregulating these pathways, potentially affecting endothelial cell activity.

Fig1. SVEC-10 cells were starved overnight, treated with TGFBI for 60 min.

Fig2. Plasma TGFBI concentrations in 20-week-old WT and KO mice.

Case Study 2: Laura S M Lecker, 2021

This study examines the transformation of the extracellular matrix (ECM) during the progression of serous tubal intraepithelial carcinoma (STIC) to high-grade serous ovarian cancer (HGSOC). Normal fallopian tubes had lower stiffness than ovaries and that STIC lesions had high levels of the ECM protein TGFBI, mainly produced by macrophages. TGFBI expression was induced by TGFβ and IL4 in macrophages and was associated with alternatively activated macrophage signatures in HGSOC. Fibroblasts in HGSOC metastases also expressed TGFBI, which could stimulate macrophage production of TGFBI. Treating HGSOC tumors with an anti-TGFBI antibody reduced tumor size and activated certain immune cells. TGFBI appears to contribute to an immunosuppressive microenvironment in STIC and may be a therapeutic target in HGSOC.

Fig3. Modified Allred scoring of the matrisome protein TGFBI.

Fig4. Western blot analysis of TGFBI in cytokine-stimulated monocyte-derived macrophages.

TGFBI has several biochemical functions, for example, collagen binding,extracellular matrix binding,integrin binding. Some of the functions are cooperated with other proteins, some of the functions could acted by TGFBI itself. We selected most functions TGFBI had, and list some proteins which have the same functions with TGFBI. You can find most of the proteins on our site.

TGFBI 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 TGFBI here. Most of them are supplied by our site. Hope this information will be useful for your research of TGFBI.

FAM9B