ヤマグチ　ヨウコ   Yamaguchi Yoko   山口　陽子    所属   東邦大学  薬学部 薬学科    職種   助教
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Pleckstrin homology-like domain family A, member 3 (PHLDA3) deficiency improves islets engraftment through the suppression of hypoxic damage
掲載誌名	正式名：PLOS ONE ISSNコード：/1932-6203
掲載区分	国外
出版社	Public Library of Science (PLoS)
巻・号・頁	12(11),pp.e0187927-e0187927
著者・共著者	Naoaki Sakata,Yohko Yamaguchi,Yu Chen,Masayuki Shimoda,Gumpei Yoshimatsu,Michiaki Unno,Shoichiro Sumi,Rieko Ohki
担当区分	2nd著者
発行年月	2017/11/09
概要	Islet transplantation is a useful cell replacement therapy that can restore the glycometabolic function of severe diabetic patients. It is known that many transplanted islets failed to engraft, and thus, new approaches for overcoming graft loss that may improve the outcome of future clinical islet transplantations are necessary. Pleckstrin homology-like domain family A, member 3 (PHLDA3) is a known suppressor of neuroendocrine tumorigenicity, yet deficiency of this gene increases islet proliferation, prevents islet apoptosis, and improves their insulin-releasing function without causing tumors. In this study, we examined the potential use of PHLDA3-deficient islets in transplantation. We observed that: 1) transplanting PHLDA3-deficient islets into diabetic mice significantly improved their glycometabolic condition, 2) the improved engraftment of PHLDA3-deficient islets resulted from increased cell survival during early transplantation, and 3) Akt activity was elevated in PHLDA3-deficient islets, especially under hypoxic conditions. Thus, we determined that PHLDA3-deficient islets are more resistant against stresses induced by islet isolation and transplantation. We conclude that use of islets with suppressed PHLDA3 expression could be a novel and promising treatment for improving engraftment and consequent glycemic control in islet transplantation.
DOI	10.1371/journal.pone.0187927
PMID	29121094
PermalinkURL	http://dx.plos.org/10.1371/journal.pone.0187927