| 2001 |
NPNT (POEM) was identified as a novel extracellular matrix adhesion molecule containing five EGF-like domains, an RGD cell-binding motif, and a MAM domain. Recombinant POEM protein promoted cell adhesion, spreading, and survival. Mutation of the RGD sequence to RGE significantly decreased cell spreading and survival activities, while the MAM domain contributed only to cell adhesion and not spreading/survival. NPNT was identified as a ligand for α8β1 integrin: KA8 cells (K562 stably expressing α8 integrin) showed strong binding and spreading on NPNT, whereas parental K562 cells (expressing α5β1) did not bind NPNT. |
Bacterial recombinant protein production, site-directed mutagenesis (RGD→RGE), cell adhesion/spreading assays, stable integrin-expressing cell lines (K562/KA8) |
The Journal of biological chemistry |
High |
11546798
|
| 2007 |
TGF-β strongly inhibited NPNT (POEM) gene expression in mouse osteoblastic MC3T3-E1 cells in a time- and dose-dependent manner. This suppression was mediated through activation of TGF-β receptor I and the ERK1/2 and JNK (c-Jun N-terminal kinase) signaling pathways. |
Gene expression analysis in MC3T3-E1 osteoblastic cells with TGF-β treatment, pathway inhibitor experiments targeting TGF-β receptor I, ERK1/2, and JNK |
FEBS letters |
Medium |
17977532
|
| 2011 |
TNF-α strongly inhibited NPNT (POEM) expression in MC3T3-E1 osteoblastic cells in a time- and dose-dependent manner through the NF-κB signaling pathway. Over-expression of NPNT rescued TNF-α-induced inhibition of osteoblast differentiation, establishing NPNT as a positive regulator of osteoblast differentiation downstream of TNF-α/NF-κB. |
Gene expression analysis in MC3T3-E1 cells with TNF-α treatment, NF-κB pathway inhibition, NPNT overexpression rescue experiment |
Biochemical and biophysical research communications |
Medium |
21689636
|
| 2016 |
NPNT is expressed by osteoblasts and functions as a paracrine angiogenic factor. Exogenous recombinant NPNT stimulated endothelial cell migration and tube-like structure formation in vitro, and promoted angiogenesis in an ex vivo fetal mouse metatarsal assay. NPNT activated phosphorylation of ERK1/2 and p38 MAPK in endothelial cells; pharmacological inhibition of ERK1/2 blocked NPNT-induced endothelial migration, tube formation, and angiogenesis, placing ERK1/2 downstream of NPNT in angiogenic signaling. |
Recombinant protein treatment of endothelial cells, migration assay, tube formation assay, ex vivo metatarsal angiogenesis assay, kinase phosphorylation assays, ERK1/2 inhibitor rescue experiments |
Scientific reports |
Medium |
27782206
|
| 2017 |
NPNT is identified as a secreted extracellular matrix protein expressed exclusively around aldosterone-producing glomeruli in normal adrenal zona glomerulosa (ZG) and in ZG-like aldosterone-producing adenomas (APAs). NPNT production is regulated by the canonical Wnt signaling pathway (highest expression in APAs with gain-of-function CTNNB1 mutations). NPNT overexpression increased aldosterone production while NPNT silencing reduced aldosterone, and NPNT exhibited pro-adhesive activity in primary adrenal and APA cells, with binding to cell-surface integrins proposed to stimulate cell-cell contact within glomeruli. |
Immunohistochemistry, NPNT overexpression and siRNA silencing in adrenal/APA cells with aldosterone readout, microarray gene expression analysis |
Hypertension (Dallas, Tex. : 1979) |
Medium |
28416583
|
| 2020 |
A COPD-associated SNP (rs34712979) creates a cryptic splice acceptor site in NPNT, resulting in inclusion of a 3-nucleotide exon extension encoding a serine residue near the N-terminus of the protein. Long-read sequencing identified 13 NPNT isoforms, 6 predicted to be protein coding, with two full-length isoforms differing only in this serine-encoding extension. Colocalisation analysis showed this splicing variant underlies COPD risk, spirometric lung function measures, and NPNT splicing (posterior probability 94%). |
Splice quantitative trait locus (sQTL) analysis, short-read RNA sequencing, Oxford Nanopore Technologies long-read sequencing, colocalization analysis with GWAS, RT-PCR |
medRxiv (preprint)preprint |
Medium |
33173926
|
| 2022 |
Down-regulation of NPNT via siRNA transfection in hepatocellular carcinoma (HCC) cells inhibited cell migration and invasion, and suppressed the FAK/PI3K/AKT signaling pathway, identifying NPNT as a regulator of HCC metastasis acting through this pathway. |
siRNA knockdown, wound healing assay, Matrigel Transwell invasion assay, western blot for FAK/PI3K/AKT pathway |
Gene |
Medium |
35304239
|
| 2022 |
A homozygous null (nonsense) variant in NPNT causes autosomal recessive bilateral renal agenesis in humans, confirmed by detection of complete nonsense-mediated decay of the NPNT transcript, establishing that complete loss of NPNT function can cause failure of kidney development (renal agenesis). |
Genome-wide linkage analysis, exome sequencing, RT-PCR demonstrating nonsense-mediated mRNA decay, Sanger sequencing for segregation |
Clinical genetics |
Medium |
35246978
|
| 2025 |
NPNT acts as an antiaging/antifibrotic molecule in the lung via interaction with integrin α3 (ITGA3). NPNT deficiency exacerbates bleomycin-induced senescence in alveolar epithelial cells and worsens fibrosis, while NPNT overexpression in alveolar epithelium improves lung function and resistance to aging and fibrosis. Mechanistically, NPNT inhibits hyperactivation of LATS1 and MOB1, facilitates YAP1 nuclear translocation, and suppresses YAP1 ubiquitination and degradation contingent on NPNT–ITGA3 interaction. Pharmacological elevation of NPNT protein levels with Escin alleviated pulmonary fibrosis in mice. |
NPNT knockout and overexpression mouse models, bleomycin-induced fibrosis assay, western blotting for LATS1/MOB1/YAP1 pathway, ubiquitination assay, pharmacological intervention (Escin) |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
Medium |
40444575
|
| 2025 |
The COPD-risk allele rs34712979-A causes a shift in NPNT isoform usage away from the dominant isoform B (excludes exon 3) to isoform A (includes exon 3). AlphaFold protein structural analysis reveals that inclusion of exon 3 disrupts an EGF-like functional domain in NPNT, providing a structural mechanism for how this splicing change impairs NPNT function and increases COPD risk. |
Long-read RNA sequencing, sQTL analysis, colocalization with COPD GWAS, AlphaFold in silico protein structural analysis |
The European respiratory journal |
Medium |
39978861
|
| 2017 |
Suppression of nephronectin (NPNT) expression by microRNA-378a-3p in zebrafish and mice significantly induced proteinuria due to loss of integrity of the glomerular filtration barrier, demonstrating that the miR-378a-3p/nephronectin axis regulates podocyte–glomerular basement membrane interaction and glomerular filtration barrier integrity. |
microRNA overexpression in zebrafish and mice, proteinuria measurement, glomerular filtration barrier integrity assessment |
Kidney international |
Medium |
28938947
|
| 2022 |
miR-378 directly targets NPNT in A549 human alveolar epithelial cells. miR-378 overexpression increased cell proliferation, migration, and suppressed apoptosis; miR-378 is upregulated while NPNT is downregulated in COPD lung tissues, suggesting a regulatory axis relevant to COPD pathogenesis. |
miR-378 overexpression in A549 cells, bioinformatics target prediction confirmed by cell functional assays (CCK-8, colony formation, Transwell, flow cytometry), analysis of public COPD expression data |
PeerJ |
Low |
36128198
|