A possible function of &lt;i&gt;Nik-related kinase&lt;/i&gt; in the labyrinth layer of delayed delivery mouse placentas

Yomogita, Hiroshi; Ito, Hikaru; Hashimoto, Kento; Kudo, Akihiko; Fukushima, Toshiaki; Endo, Toshihiko; Hirate, Yoshikazu; Akimoto, Yoshihiro; Komada, Masayuki; Kanai, Yoshikatsu; Miyasaka, Naoyuki; Kanai‐Azuma, Masami

doi:10.1262/jrd.2022-120

Cited by 3 publications

(1 citation statement)

References 30 publications

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“…In the human placenta, NRK is expressed in cytotrophoblasts and syncytiotrophoblasts in villi (21), which share similar functions to the mouse spongiotrophoblast and labyrinth layers, respectively (1, 22, 23). Nrk KO mice showed placental hyperplasia with a much enlarged spongiotrophoblast layer and moderately enlarged labyrinth layer (19, 24), demonstrating the role of NRK in preventing excessive placenta growth.…”

Section: Introductionmentioning

confidence: 99%

The placental protein NRK promotes cell death through its plasma membrane-localizing CNH domain

Lestari,

Soda,

Moritsugu

et al. 2023

Preprint

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Placental development is regulated by the balance between cell proliferation and death. The placental protein NRK (NIK-related kinase) plays a role in preventing excessive placenta growth. We previously demonstrated that NRK underwent rapid molecular evolution in the ancestor of placental mammals and acquired the functional regions, including the phospholipid-binding citron homology (CNH) domain, by which NRK inhibits cell proliferation. NRK is also potentially responsible for cell death; caspases cleave NRK during apoptosis, releasing theC-terminal fragment that promotes cell death. Here, we explored the molecular mechanisms underlying the cell death-promoting effects of NRK. Our experimental data using HeLa, placenta trophoblast BeWo (human), and Rcho-1 (rat) cells indicated that the CNH domain of NRK was required and sufficient to promote cell death.In vitroandin silicostudies showed the NRK CNH domain bound to phospholipids via its polybasic clusters and remains at the plasma membrane (PM) during apoptosis. Evolutional analyses indicated that these clusters formed in the ancestor of placental mammals. Mutations in these clusters (CNH-18A) hindered the cell death-promoting activity of the CNH domain. We concluded that NRK promotes cell death through its plasma membrane-localizing CNH domain and suggested its active role in PM-associated events during cell death.

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Section: Introductionmentioning

confidence: 99%

The placental protein NRK promotes cell death through its plasma membrane-localizing CNH domain

Lestari,

Soda,

Moritsugu

et al. 2023

Preprint

Self Cite

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Chronic non-discriminatory social defeat stress during the perinatal period induces depressive-like outcomes in female mice

Ito,

Miyoshi

et al. 2024

Brain Research

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Identification and functional activity of Nik related kinase (NRK) in benign hyperplastic prostate

He,

Tian,

Dong

et al. 2024

J Transl Med

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Objective Benign prostatic hyperplasia (BPH) is common in elder men. The current study aims to identify differentially expressed genes (DEGs) in hyperplastic prostate and to explore the role of Nik related kinase (NRK) in BPH. Methods Four datasets including three bulk and one single cell RNA-seq (scRNA-seq) were obtained to perform integrated bioinformatics. Cell clusters and specific metabolism pathways were analyzed. The localization, expression and functional activity of NRK was investigated via RT-PCR, western-blot, immunohistochemical staining, flow cytometry, wound healing assay, transwell assay and CCK-8 assay. Results A total of 17 DEGs were identified by merging three bulk RNA-seq datasets. The findings of integrated single-cell analysis showed that NRK remarkably upregulated in fibroblasts and SM cells of hyperplasia prostate. Meanwhile, NRK was upregulated in BPH samples and localized almost in stroma. The expression level of NRK was significantly correlated with IPSS and Qmax of BPH patients. Silencing of NRK inhibited stromal cell proliferation, migration, fibrosis and EMT process, promoted apoptosis and induced cell cycle arrest, while overexpression of NRK in prostate epithelial cells showed opposite results. Meanwhile, induced fibrosis and EMT process were rescued by knockdown of NRK. Furthermore, expression level of NRK was positively correlated with that of α-SMA, collagen-I and N-cadherin, negatively correlated with that of E-cadherin. Conclusion Our novel data identified NRK was upregulated in hyperplastic prostate and associated with prostatic stromal cell proliferation, apoptosis, cell cycle, migration, fibrosis and EMT process. NRK may play important roles in the development of BPH and may be a promising therapeutic target for BPH/LUTS.

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A possible function of <i>Nik-related kinase</i> in the labyrinth layer of delayed delivery mouse placentas

Cited by 3 publications

References 30 publications

The placental protein NRK promotes cell death through its plasma membrane-localizing CNH domain

The placental protein NRK promotes cell death through its plasma membrane-localizing CNH domain

Chronic non-discriminatory social defeat stress during the perinatal period induces depressive-like outcomes in female mice

Identification and functional activity of Nik related kinase (NRK) in benign hyperplastic prostate

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