Identification of the protective mechanisms of Lactoferrin in the irradiated salivary gland

Sakai, Manabu; Matsushita, Takumi; Hoshino, Ryoko; Ono, Hisayo; Ikai, Kazuki; Sakai, Takayoshi

doi:10.1038/s41598-017-10351-9

Cited by 22 publications

(22 citation statements)

References 55 publications

(84 reference statements)

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“…The SMGs were separated from embryonic ICR mice (Japan SLC, Inc. Hamamatsu, Japan) and cultured on Nucleopore membranes (1 µm pore size; GE Healthcare UK Ltd, Buckinghamshire, UK) in serum-free Dulbecco's modified Eagle's medium/ F12 medium, as described previously [20,22]. The protocol was agreed by the Committee on the Ethics of Animal Experiments of Osaka University Graduate School of Dentistry (permit number: 25-004-0).…”

Section: Submandibular Salivary Gland Culturementioning

confidence: 99%

“…LY294002 was assayed at the concentration described previously [22]. LY294002 was assayed at the concentration described previously [22].…”

Section: Inhibitor Treatmentmentioning

confidence: 99%

“…All surgeries were performed using sodium pentobarbital anesthesia, and all efforts were applied to minimize animal suffering. The SMGs were separated from embryonic ICR mice (Japan SLC, Inc. Hamamatsu, Japan) and cultured on Nucleopore membranes (1 µm pore size; GE Healthcare UK Ltd, Buckinghamshire, UK) in serum-free Dulbecco's modified Eagle's medium/ F12 medium, as described previously [20,22]. E13.5 SMGs were cultured for 12 h after removal from pregnant mice to recover from injury during the operation.…”

Section: Submandibular Salivary Gland Culturementioning

confidence: 99%

“…Organ branching morphogenesis starts from a simple epithelial bud at E12 to eventually develop into a polycystic structure [20]. We previously used ex vivo submandibular salivary gland (SMG) organ culture [21,22] to better observe SMG branching morphogenesis in E13-E15. The majority of the branching occurs at embryonic day (E) 13-E15.…”

Section: Introductionmentioning

confidence: 99%

“…The majority of the branching occurs at embryonic day (E) 13-E15. We previously used ex vivo submandibular salivary gland (SMG) organ culture [21,22] to better observe SMG branching morphogenesis in E13-E15. This method has been used for various experiments that investigate cell-cell interactions, cellmatrix interactions, cell migration, cell proliferation and cell death, etc.…”

Section: Introductionmentioning

confidence: 99%

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Role of the mTOR signalling pathway in salivary gland development

et al. 2019

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Development of the salivary gland is characterized by extensive branching morphogenesis. Although various molecules have been implicated in salivary gland development, the role of the mammalian target of rapamycin (mTOR) signalling pathway, including both mTOR complexes 1 and 2 (mTORC1 and 2), in salivary gland development is unknown. Here, we examined protein expression levels related to the mTOR signalling pathway using an ex vivo submandibular salivary gland (SMG) organ culture. We showed that branching buds in the salivary glands were substantially decreased and phosphorylation of mTORC1 signalling pathway related proteins (mTOR, p70 ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E‐binding protein 1) was inhibited by rapamycin (an mTOR inhibitor). In addition, AKT, which is an upstream protein kinase of mTORC1 and is downstream of mTORC2, is inhibited by LY294002 (a phosphatidylinositol 3‐kinase inhibitor), but not by rapamycin. Moreover, rapamycin‐treated ICR neonatal mice exhibited a reduction in both body weight and salivary glands compared with vehicle‐treated neonatal mice. The present data indicate that the mTOR signalling pathway, including both mTORC1 and mTORC2, plays a critical role in salivary gland development both in ex vivo SMG organ culture and ICR neonatal mice in vivo.

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Section: Submandibular Salivary Gland Culturementioning

confidence: 99%

“…LY294002 was assayed at the concentration described previously [22]. LY294002 was assayed at the concentration described previously [22].…”

Section: Inhibitor Treatmentmentioning

confidence: 99%

Section: Submandibular Salivary Gland Culturementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of the mTOR signalling pathway in salivary gland development

et al. 2019

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ΔNp63 is upregulated during salivary gland regeneration following duct ligation and irradiation in mice

et al. 2020

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The transcription factor p63, a component of the p53 family, has important functions in development, homeostasis, and regeneration of epithelial tissues. However, the role of p63 in the regeneration of exocrine glands, including the salivary glands (SGs), has not been fully investigated. We investigated p63 expression in SG regeneration induced by duct ligation and irradiation. The expression of DNp63, a p63 isoform, increased and was colocalized with keratin 5 positive cells were myoepithelial cells. Furthermore, DNp63 expression was regulated by FGF7 stimulation via p38 MAPK phosphorylation and affected SG morphogenesis. These results suggest that DNp63 is essential for SG regeneration and may be a new target for regenerative treatment.

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The HIF‐1α pathway plays a critical role in salivary gland development in ex vivo organ cultures

et al. 2021

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The transcription factor, hypoxia‐inducible factor‐1α (HIF‐1α), has previously been shown to upregulate the expression of hypoxia‐related genes, including erythropoietin (EPO). However, the role of hypoxia‐inducible factor‐1α in morphogenesis during salivary gland development is unclear. We investigated the function of HIF‐1α in submandibular gland (SMG) organ cultures obtained from embryonic day 13.5 embryos from ICR female mice. Expression of HIF‐1α, glucose transporter 1, and vascular endothelial growth factor was induced under hypoxia (5% O2). We further showed that BAY 87‐2243‐mediated inhibition of HIF‐1α suppressed salivary gland development. Under severe hypoxia (1% O2), HIF‐1α did not promote salivary gland development; this was due to suppression of cell proliferation and inhibition of the cell cycle and not because of autophagy and apoptosis. Additionally, using the inhibitor U0126, we verified that the ERK1/2 pathway is upstream of HIF‐1α. Overall, we found that the HIF‐1α signaling pathway plays a critical role in salivary gland development in ex vivo SMG organ cultures.

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Identification of the protective mechanisms of Lactoferrin in the irradiated salivary gland

Cited by 22 publications

References 55 publications

Role of the mTOR signalling pathway in salivary gland development

Role of the mTOR signalling pathway in salivary gland development

ΔNp63 is upregulated during salivary gland regeneration following duct ligation and irradiation in mice

The HIF‐1α pathway plays a critical role in salivary gland development in ex vivo organ cultures

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