FBLN5

Official Full Name

fibulin 5

Organism

Homo sapiens

GeneID

10516

Background

The protein encoded by this gene is a secreted, extracellular matrix protein containing an Arg-Gly-Asp (RGD) motif and calcium-binding EGF-like domains. It promotes adhesion of endothelial cells through interaction of integrins and the RGD motif. It is prominently expressed in developing arteries but less so in adult vessels. However, its expression is reinduced in balloon-injured vessels and atherosclerotic lesions, notably in intimal vascular smooth muscle cells and endothelial cells. Therefore, the protein encoded by this gene may play a role in vascular development and remodeling. Defects in this gene are a cause of autosomal dominant cutis laxa, autosomal recessive cutis laxa type I (CL type I), and age-related macular degeneration type 3 (ARMD3). [provided by RefSeq, Jul 2008]

Synonyms

EVEC; UP50; ADCL2; ARMD3; CMT1H; DANCE; ARCL1A; FIBL-5; HNARMD;

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Detailed Information

Pin-pin protein-5 (FBLN-5) is an extracellular matrix glycoprotein that is widely distributed in tissues rich in elastic protein. It can adjust the structure of the matrix by interacting with other extracellular proteins. Recent studies have found that this protein is an endogenous angiogenesis inhibitor and plays an important role in vascular development. In addition, pin button protein-5 is related to the proliferation, metastasis and invasion of some tumors, and its gene mutations can lead to the occurrence of genetic diseases.

FBLN-5 and Angiogenesis

Studies have found that the content of FBLN-5 in adult blood vessels is very low, but the content is significantly increased in the case of vascular development and vascular damage, suggesting that it is an angiogenesis-related protein. Knockout experiments of FBLN-5 showed that the protein is involved in the assembly of elastic fibers and is related to maintaining the normal function of the lumen. Researchers explored the possible function of FBLN-5 on vascular endothelial cells. They found that transfection or the addition of FBLN-5 protein can significantly reduce the proliferation, invasion and luminal formation of mouse brain microvascular endothelial cells. In addition, in the transwell experiment, FBLN-5 protein can also inhibit the migration of human microvascular endothelial cells to fibronectin (FN). Researchers also found that the proliferation ability of bovine pulmonary artery endothelial cells was significantly weakened after adding FBLN-5 protein. The above experiments show that FBLN-5 has an inhibitory effect on endothelial cell proliferation, invasion, migration and lumen formation.

Figure 1. Models of elastic fiber assembly in Ltbp4S-/-and Fbln5-/-. (Dabovic, B., et al. 2015)

Researchers explored the possible effects of FBLN-5 on smooth muscle cells, another important cell in the angiogenesis process. By culturing smooth muscle cells from FBLN-5-/-mice, they found that under the stimulation of plateletderived growth factor (PDGF), the proliferation and migration ability of the cells was significantly enhanced compared to normal smooth muscle cells. However, overexpression of FBLN-5 will suppress this increasing trend. Subsequent studies have confirmed that FBLN-5 can bind to the integrins on the surface of human smooth muscle cells through the RGD model, and inhibit cell adhesion and migration mediated by FN. It can be seen that FBLN-5 has an inhibitory effect on the proliferation and migration of two types of important cells in the process of vascular growth-endothelial cells and smooth muscle cells, suggesting that it may be an angiogenesis inhibitor.

FBLN-5 and Tumor

In fibroblasts and epithelial cells, transforming growth factor β (TGF-β) can significantly promote the expression of FBLN-5. Since epithelial cells are the main source of most tumor cells, and TGF-β plays a key role in the process of epithelial cell deterioration, it is speculated that the changes in FBLN-5 expression may be related to the tumorigenesis process. In order to further explore the relationship between FBLN-5 and tumors, the researchers used radioactive cDNA probe hybridization technology to detect 25 metastatic tumor samples and found that the mRNA level of FBLN-5 in 17 samples was down-regulated, and no one was up-regulated. This down-regulation trend is particularly obvious in malignant tumors such as kidney cancer, breast cancer, ovarian cancer, and colon cancer, suggesting that the inactivation of FBLN-5 is involved in the related process of cancer.

In the process of lung cancer, the expression of MMP-7 will increase, which will promote the invasion of lung cancer cells. Research has shown that FBLN-5 can bind to integrins through its RGD motif to down-regulate the ERK1/2 pathway, and then down-regulate the expression of MMP-7, and ultimately exert the function of inhibiting lung cancer cell invasion. At the same time, the mouse model also confirmed that FBLN-5 can effectively inhibit lung cancer metastasis. In addition to down-regulating the expression of MMP-7, FBLN-5 can also down-regulate the expression of MMP-2, MMP-3, and up-regulate the expression of TIMP-1 and TIMP-3 during angiogenesis, indicating that FBLN-5 and MMP/TIMP protein family have a broad association.

References:

Dabovic, B., Robertson, I. B., Zilberberg, L., Vassallo, M., Davis, E. C., & Rifkin, D. B. (2015). Function of latent TGFβ binding protein 4 and fibulin 5 in elastogenesis and lung development. Journal of Cellular Physiology, 230(1), 226-236.
Van Maldergem, L., & Loeys, B. (1993). FBLN5-Related Cutis Laxa. In M. P. Adam (Eds.) et al., GeneReviews®. University of Washington, Seattle.
Shin, S. J., & Yanagisawa, H. (2019). Recent updates on the molecular network of elastic fiber formation. Essays in biochemistry, 63(3), 365–376.

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