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It is therefore important to manage such irradiation to prevent damage to the salivary glands. A previous study showed that Lactoferrin (LF) has a radioprotective effect, but the mechanism was not determined in salivary glands. In the present study, we investigated the detailed radioprotective effect of LF using both<jats:italic>ex vivo<\/jats:italic>submandibular salivary gland organ culture and ICR male mice<jats:italic>in vivo<\/jats:italic>. We found that LF had effects on both cell proliferation and CyclinD1-mediated cell-cycle progression which were regulated via the ERK1\/2 and AKT signal transduction pathways. In addition, LF affected acinar cell structure and function after irradiation. These findings suggest that LF may be a useful agent to prevent irradiation effects in salivary glands.<\/jats:p>","DOI":"10.1038\/s41598-017-10351-9","type":"journal-article","created":{"date-parts":[[2017,8,23]],"date-time":"2017-08-23T08:53:26Z","timestamp":1503478406000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Identification of the protective mechanisms of Lactoferrin in the irradiated salivary gland"],"prefix":"10.1038","volume":"7","author":[{"given":"Manabu","family":"Sakai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takumi","family":"Matsushita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryoko","family":"Hoshino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitomi","family":"Ono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuki","family":"Ikai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayoshi","family":"Sakai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,8,29]]},"reference":[{"key":"10351_CR1","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1067\/mpr.2001.113778","volume":"85","author":"SP Humphrey","year":"2001","unstructured":"Humphrey, S. 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