NPNT

Official Full Name

nephronectin

Organism

Homo sapiens

GeneID

255743

Background

Predicted to enable integrin binding activity. Predicted to be involved in several processes, including cell-cell adhesion mediated by integrin; positive regulation of ERK1 and ERK2 cascade; and positive regulation of alkaline phosphatase activity. Predicted to act upstream of or within positive regulation of transforming growth factor beta receptor signaling pathway. Located in collagen-containing extracellular matrix and extracellular exosome. [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

POEM; EGFL6L;

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Detailed Information

Nephronectin (NPNT), also known as POEM (preosteoblast epidermal growth factor-like repeat protein with meprin) or EGFL6L, is a new type of extracellular matrix found in mouse embryo kidneys, with a molecular weight of 70 ~ 90 kDa. It is a new ligand for integrin α8β1. The NPNT gene is located on chromosome 4q24 and contains 13 exons. Its transcriptional expression is of great significance in physiological functions such as cell proliferation, differentiation, adhesion, apoptosis, and metabolism and in the pathological processes of various tissues or organ diseases.

NPNT is involved in human development and is expressed in multiple organs and tissues of embryos, newborns, and adults, such as embryonic urogenital spinal ureteral epithelial cells. NPNT mRNA was age-related. On day 13.5 of embryonic development (E13.5), NPNT was expressed in choroid plexus, jaw, ectoderm, developing teeth, lung basal layer, stomach, esophagus, ear and other tissues and organs. In newborns, NPNT is also expressed in the lens and taste buds; in adults, NPNT is expressed in the kidney, lung, brain, blood vessels, and thyroid.

Npnt Figure 1. Regulation of nephronectin gene expression by TGF-β, TNF-a and OSM. （Yamada A, et al. 2016）

NPNT and Tumor

Studies have shown that NPNT expression is reduced in mouse metastatic breast cancer models and is associated with organ metastasis. NPNT was expressed in the lung and liver tissues of the control animals, but the NPNT expression was lost in the metastatic tumors on the 25th day, suggesting that the NPNT deletion may help to form a metastatic environment for cancer cells. However, other researchers have established a spontaneous bone metastasis model of breast cancer and analyzed the role of extracellular matrix NPNT through genomic analysis, and found that it is specifically expressed in highly metastatic tumor epithelial cells. Inhibition of NPNT expression can significantly reduce the spontaneous metastasis of tumor cells in the lung, bone, and kidney.

Steigedal et al. comprehensively analyzed the expression pattern and distribution of NPNT in tissue microarrays of 842 breast cancer patients, and found that there was a correlation between cytoplasmic particle staining (<10% of tumor cells) and poor prognosis. NPNT promotes adhesion and anchoring independent growth through its integrin binding and enhancer motifs, and promotes the colonization of breast tumor cells in the lung, suggesting that NPNT may be a new type of prognostic indicator for breast cancer patients. Studies have shown that NPNT is reduced or absent in most melanoma cell lines and malignant melanoma tissues. NPNT increases cell adhesion and reduces cell migration and invasion, while NPNT deletion promotes tumor progression.

NPNT and Kidney Disease

Studies have shown that NPNT continues to be highly expressed during kidney development, while NPNT or integrin α8β1 knockout mice often show renal dysgenesis or organ defects, suggesting that NPNT may participate in kidney development by binding integrin α8β1. The expression of glial cell line-derived neurotrophic factor (Gdnf) in NPNT gene knockout mice decreased significantly, suggesting that NPNT gene can activate Gdnf.

The researchers studied 190 biopsy specimens of different types of kidney disease and found that NPNT was highly expressed in the dilated mesangial matrix of 18 patients with diabetic nephropathy. In addition, it is negatively expressed in other kidney diseases (eg, IgA glomerulonephritis, membranoproliferative glomerulonephritis, lupus nephritis, and membranous glomerulonephritis). This result suggests that NPNT can assist the diagnosis of diabetic nephropathy. Studies have shown that NPNT may participate in the pathophysiology of acute tubular necrosis cell regeneration and repair, and promote renal tubular epithelial cell proliferation. The increased expression of NPNT in acute tubular necrosis and regenerating renal tubular epithelial cells during the recovery period suggests that NPNT may be a potential biomarker.

References:

Steigedal, T. S., Toraskar, J., Redvers, R. P., Valla, M., Magnussen, S. N., Bofin, A. M., ... & Doherty, J. (2018). Nephronectin is correlated with poor prognosis in breast cancer and promotes metastasis via its integrin-binding motifs. Neoplasia, 20(4), 387-400.
Zimmerman, S. E. , Hiremath, C. , Tsunezumi, J. , Yang, Z. , Finney, B. , & Marciano, D. K. . (2018). Nephronectin regulates mesangial cell adhesion and behavior in glomeruli. Journal of the American Society of Nephrology, 29(4), ASN.2017070752.
Yamada A，Kamijo R. (2016). Nephronectin: An Extracellular Matrix Protein with Diverse Functions. Journal of dentistry &disorders, 2(1): 1004.

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