<scp>FGF</scp>‐2 suppresses expression of nephronectin via <scp>JNK</scp> and <scp>PI</scp>3K pathways

Kato, Tadashi; Yamada, Atsushi; Ikehata, Mikiko; Yoshida, Yuko; Sasa, Kiyohito; Morimura, Naoko; Sakashita, Akihiko; Iijima, Takehiko; Chikazu, Daichi; Ogata, Hiroaki; Kamijo, Ryutaro

doi:10.1002/2211-5463.12421

Cited by 7 publications

(4 citation statements)

References 31 publications

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“…More recently, it was reported that Npnt is a potential prognostic marker in breast cancer and that Npnt mediates p38 mitogen-activated protein kinase (MAPK)–induced cell viability [38]. Npnt expression was suppressed by fibroblast growth factor (FGF)-2 via c-Jun N-terminal kinase (JNK) in MAPK and Phosphoinositide 3-kinase (PI3K) pathways [39]. However, no correlations have been reported in the case of lung fibrosis.…”

Section: Silicosis and Integrinmentioning

confidence: 99%

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Role of Nephronectin in Pathophysiology of Silicosis

Lee

Honda

Yamamoto

et al. 2019

IJMS

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Silicosis is a typical form of pneumoconiosis and is characterized as a type of lung fibrosis. Silica particles are captured and recognized upon by alveolar macrophages via the macrophage receptor with collagenous structure (MARCO) scavenger receptor, and thereafter the inflammasome is activated. Thereafter, various chemokines/cytokines play their roles to eventually form fibrosis. Additionally, silica particles chronically activate T helper cells which sets the background for the formation of silicosis-associated autoimmune disturbances. The occurrence and progression of lung fibrosis, the extracellular matrix-related molecules such as integrins and their ligands including fibronectin, vitronectin, laminin, and collagens, all play important roles. Here, the roles of these molecules in silicosis-related lung fibrosis are reviewed from the literature. Additionally, the measurement of serum nephronectin (Npnt), a new member of the integrin family of ligands, is discussed, together with investigations attempting to delineate the role of Npnt in silica-induced lung fibrosis. Serum Npnt was found to be higher in silicosis patients compared to healthy volunteers and seems to play a role in the progression of fibrosis with other cytokines. Therefore, serum Npnt levels may be employed as a suitable marker to monitor the progression of fibrosis in silicosis patients.

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Section: Silicosis and Integrinmentioning

confidence: 99%

“…However, it has been indicated that profibrotic growth factors such as FGF-2 [39] and TGF-β [69,70] and the profibrotic JAK/STAT pathway [70] suppress the expression of Npnt. These investigations focused on osteogenesis.…”

Section: Npnt In Silicosismentioning

confidence: 99%

Role of Nephronectin in Pathophysiology of Silicosis

Lee

Honda

Yamamoto

et al. 2019

IJMS

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“…GROUP 1 PSENEN, CXCR1 [5] GROUP 2 BMP6, SMAD3 [19] BMP6, MAPK1 [96] MAPK1, SMAD3 [26] MAPK1, MAPT [51] MAPK1, PRKCQ [15] GROUP 3 ASXL2, BIRC6 [43] GROUP 4 FGFR1, TGFBR3 [88] FGFR1, NPNT [41] GROUP 5 BMP4, MMP10 [27] BMP4, HSD17B1 [4] 9 Data from https://www.kaggle.com/datasets/raghadalharbi/ breast-cancer-gene-expression-profiles-metabric…”

Section: Group Features Refmentioning

confidence: 99%

Composite Feature Selection using Deep Ensembles

Imrie¹,

Alexander²,

Lió³

et al. 2022

Preprint

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In many real world problems, features do not act alone but in combination with each other. For example, in genomics, diseases might not be caused by any single mutation but require the presence of multiple mutations. Prior work on feature selection either seeks to identify individual features or can only determine relevant groups from a predefined set. We investigate the problem of discovering groups of predictive features without predefined grouping. To do so, we define predictive groups in terms of linear and non-linear interactions between features. We introduce a novel deep learning architecture that uses an ensemble of feature selection models to find predictive groups, without requiring candidate groups to be provided. The selected groups are sparse and exhibit minimum overlap. Furthermore, we propose a new metric to measure similarity between discovered groups and the ground truth. We demonstrate the utility of our model on multiple synthetic tasks and semi-synthetic chemistry datasets, where the ground truth structure is known, as well as an image dataset and a real-world cancer dataset.

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“…Tumour necrosis factor α(TNFα) Nuclear factor-κB (NF-κB) [62] Transforming growth factor β(TGF-β) ALK5, Smad2 ERK1/2, JNK, MAPK [23,63,64] Fibroblast growth factor-2 (FGF-2) JNK PI3K [65] Interleukin-1β(IL-1β) JNK ERK1/2 [66] Oncostatin M (OSM) JAK/STAT MAPK [67] Inorganic Phosphate FGFRs (via Pit) [68] Mmu-miRNAs 23a, 101a, 296-5p, 328, 425 GSK3β, Cyclin D, ERK [69] Up-regulation Wnt3a Wnt β-catenin, TCF/LEF [42,70,71] Bone morphogenetic protein-2 (BMP-2) [72] Vitamin D 3 Vitamin D receptor (VDR) [73] Fibroblast growth factor 10 (FGF10) transcription factor T box 5 (Tbx5) [43] Insulin growth factor (IGF) IGFR-ERK1/2 [74] ? ERK5-Sp1-Klf2/4 [75] Most studies on NPNT regulation (Table 1) are done on osteoblasts, where the protein has a central role in differentiation.…”

Section: Down-regulationmentioning

confidence: 99%

Nephronectin as a Matrix Effector in Cancer

Magnussen

Toraskar

Hadler‐Olsen

et al. 2021

Cancers

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The extracellular matrix protein nephronectin plays an important regulatory role during embryonic development, controlling renal organogenesis through integrin α8β1 association. Nephronectin has three main domains: five N-terminal epidermal growth factor-like domains, a linker region harbouring two integrin-binding motifs (RGD and LFEIFEIER), and a C-terminal MAM domain. In this review, we look into the domain-related functions of nephronectin, and tissue distribution and expression. During the last two decades it has become evident that nephronectin also plays a role during cancer progression and in particular metastasis. Nephronectin is overexpressed in both human and mouse breast cancer compared to normal breast tissue where the protein is absent. Cancer cells expressing elevated levels of nephronectin acquire increased ability to colonise distant organs. In particular, the enhancer-motif (LFEIFEIER) which is specific to the integrin α8β1 association induces viability via p38 MAPK and plays a role in colonization. Integrins have long been desired as therapeutic targets, where low efficiency and receptor redundancy have been major issues. Based on the summarised publications, the enhancer-motif of nephronectin could present a novel therapeutic target.

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FGF‐2 suppresses expression of nephronectin via JNK and PI3K pathways

Cited by 7 publications

References 31 publications

Role of Nephronectin in Pathophysiology of Silicosis

Role of Nephronectin in Pathophysiology of Silicosis

Composite Feature Selection using Deep Ensembles

Nephronectin as a Matrix Effector in Cancer

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