Expression of nephronectin is enhanced by 1α,25‐dihydroxyvitamin D<sub>3</sub>

Hiranuma, Katsuhiro; Yamada, Atsushi; Kurosawa, Tamaki; Aizawa, Ryo; Suzuki, Daisuke; Saito, Yoshiro; Nagahama, Ryo; Ikehata, Mikiko; Tsukasaki, Masayuki; Morimura, Naoko; Chikazu, Daichi; Maki, Koutaro; Shirota, Tatsuo; Miki, Takami; Yamamoto, Masahide; Iijima, Takehiko; Kamijo, Ryutaro

doi:10.1002/2211-5463.12085

Cited by 6 publications

(5 citation statements)

References 14 publications

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“…More recently, Wnt3a was reported to enhance Npnt mRNA expression in osteoblast‐like MC3T3‐E1 cells, thus increasing osteoblast differentiation via the Wnt/β‐catenin signaling pathway (Ikehata et al, ). The expression of NPNT mRNA is also enhanced in MC3T3‐E1 osteoblastic cells by the addition of 1α,25‐dihydroxyvitamin D 3 , a hormonally active metabolite of Vitamin D (Hiranuma et al, ).…”

Section: Npnt Function and Expression Regulation In Osteoblastsmentioning

confidence: 99%

The emerging role of NPNT in tissue injury repair and bone homeostasis

Sun

Kuek

Qiu

et al. 2017

Journal Cellular Physiology

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Nephronectin (NPNT), a highly conserved extracellular matrix protein, plays an important role in regulating cell adhesion, differentiation, spreading, and survival. NPNT protein belongs to the epidermal growth factor (EGF)-like superfamily and exhibits several common structural determinants; including EGF-like repeat domains, MAM domain (Meprin, A5 Protein, and Receptor Protein-Tyrosine Phosphatase µ), RGD motif (Arg-Gly-Asp) and a coiled-coil domain. It regulates integrins-mediated signaling pathways via the interaction of its RGD motif with integrin α8β1. Recent studies revealed that NPNT is involved in kidney development, renal injury repair, atrioventricular canal differentiation, pulmonary function, and muscle cell niche maintenance. Moreover, NPNT regulates osteoblast differentiation and mineralization, as well as osteogenic angiogenesis. Altered expression of NPNT has been linked with the progression of certain types of cancers, such as spontaneous breast tumor metastasis and malignant melanoma. Interestingly, NPNT gene expression can be regulated by a range of external factors such as tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), oncostatin M (OSM), bone morphogenic protein 2 (BMP2), Wnt3a, Vitamin D , and microRNA-378 (miR378). Further understanding the cellular and molecular mechanisms by which NPNT regulates tissue homeostasis in an organ-specific manner is critical in exploring NPNT as a therapeutic target for tissue regeneration and tissue engineering.

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Section: Npnt Function and Expression Regulation In Osteoblastsmentioning

confidence: 99%

The emerging role of NPNT in tissue injury repair and bone homeostasis

Sun

Kuek

Qiu

et al. 2017

Journal Cellular Physiology

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“…Npnt gene expression is seen in calcification tissues, especially in osteoblasts, thus in order to investigate osteoblast functions, we have performed experiments to elucidate the pattern of Npnt gene expression with several different reagents. In previous studies, we found that 1α,25-dihydroxyvitamin D 3 and Wnt3a promoted Npnt gene expression 8 , 9 , whereas TGF-β, TNF-α, IL-1β, OSM, FGF-2, and inorganic phosphate suppressed that expression 10 – 15 . Those results suggest that Npnt gene expression in osteoblasts is regulated via various factors.…”

Section: Introductionmentioning

confidence: 77%

Phorbol-12-myristate 13-acetate inhibits Nephronectin gene expression via Protein kinase C alpha and c-Jun/c-Fos transcription factors

Kinoshita

Yamada

Sasa

et al. 2021

Sci Rep

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Nephronectin (Npnt) is an extracellular matrix protein and ligand of integrin α8β1 known to promote differentiation of osteoblasts. A search for factors that regulate Npnt gene expression in osteoblasts revealed that phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), had a strong effect to suppress that expression. Research was then conducted to elucidate the signaling pathway responsible for regulation of Npnt gene expression by PMA in osteoblasts. Treatment of MC3T3-E1 cells with PMA suppressed cell differentiation and Npnt gene expression. Effects were noted at a low concentration of PMA, and were time- and dose-dependent. Furthermore, treatment with the PKC signal inhibitor Gö6983 inhibited down-regulation of Npnt expression, while transfection with small interfering RNA (siRNA) of PKCα, c-Jun, and c-Fos suppressed that down-regulation. The present results suggest regulation of Npnt gene expression via the PKCα and c-Jun/c-Fos pathway.

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“…(Table 4) Discussion Nephronectin is a highly conserved ECM protein that plays critical roles in regulating cell adhesion, differentiation, and survival. It acts as adhesion molecule and is involved in morphogenesis and functions of various tissues, such as the kidneys, liver, and bone [10,15].…”

Section: Resultsmentioning

confidence: 99%

Nephronectin (NPNT) and the prediction of nephrotic syndrome response to steroid treatment

Watany

El‐Horany

2018

Eur J Hum Genet

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Steroid-resistant nephrotic syndrome represents about 10-20% of pediatrics' nephrotic syndrome. The regeneration of glomerular barrier seems pivotal for cessation of proteinuria. Nephronectin (NPNT) plays a major role in nephrogenesis, signal transduction, and epithelial-mesenchymal interactions. This study aims to preliminary assess NPNT as potential noninvasive biomarker of glomerular regeneration and its ability to identify steroid resistance. In this case control study, 80 retrospectively selected patients with nephrotic syndrome were enrolled in addition to 40 healthy controls. Forty patients were steroid sensitive (SSNS) and the other 40 patients were steroid-resistant (SRNS), NPTN concentration was measured using ELISA and NPNT mRNA expression was assayed using real-time PCR. NPTN concentrations were significantly higher in SSNS than both SRNS and controls (The means were 4.64 ± 3.05, 0.69 ± 0.44, and 1.63 ± 0.59, respectively). Moreover, NPTN concentrations were significantly lower in SRNS than controls. NPTN was significantly overexpressed in SSNS compared to both SRNS and controls (the means were 10.82 ± 7.39, 1.19 ± 0.94, and 1.04 ± 0.10, respectively) with no statistically significant difference between SRNS and controls. ROC curves analysis showed that both NPNT expression and NPNT serum level are of promising diagnostic performance (ROC 0.948 and 0.896, respectively). Regression analysis showed that both NPNT expression and NPNT serum level can be independent predictors of steroid resistance. The present study shows for the first time an enhanced expression of NPNT in steroid-sensitive nephrotic syndrome patients suggesting NPNT as a marker of glomerular regeneration. Also, serum NPNT can be a useful noninvasive biomarker of steroid resistance.

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Expression of nephronectin is enhanced by 1α,25‐dihydroxyvitamin D₃

Cited by 6 publications

References 14 publications

The emerging role of NPNT in tissue injury repair and bone homeostasis

The emerging role of NPNT in tissue injury repair and bone homeostasis

Phorbol-12-myristate 13-acetate inhibits Nephronectin gene expression via Protein kinase C alpha and c-Jun/c-Fos transcription factors

Nephronectin (NPNT) and the prediction of nephrotic syndrome response to steroid treatment

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Expression of nephronectin is enhanced by 1α,25‐dihydroxyvitamin D3

Cited by 6 publications

References 14 publications

The emerging role of NPNT in tissue injury repair and bone homeostasis

The emerging role of NPNT in tissue injury repair and bone homeostasis

Phorbol-12-myristate 13-acetate inhibits Nephronectin gene expression via Protein kinase C alpha and c-Jun/c-Fos transcription factors

Nephronectin (NPNT) and the prediction of nephrotic syndrome response to steroid treatment

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Expression of nephronectin is enhanced by 1α,25‐dihydroxyvitamin D₃