Pleckstrin homology-like domain family A, member 3 (PHLDA3) deficiency improves islets engraftment through the suppression of hypoxic damage.
Pleckstrin homology-like domain family A, member 3 (PHLDA3) deficiency improves islets engraftment through the suppression of hypoxic damage.
复制标题
DOI：
10.1371/journal.pone.0187927
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Ohki R
中科院分区：
文献类型：
--
作者：
Sakata N;Yamaguchi Y;Chen Y;Shimoda M;Yoshimatsu G;Unno M;Sumi S;Ohki R
胰岛移植是一种有效的细胞替代疗法，可以恢复严重糖尿病患者的糖代谢功能。众所周知，许多移植的胰岛未能植入，因此，克服移植物丢失的新方法，可能会改善未来临床胰岛移植的结果是必要的。普列克底物蛋白同源样结构域家族A，成员3（PHLDA 3）是已知的神经内分泌致瘤性抑制因子，然而该基因的缺陷增加胰岛增殖，防止胰岛凋亡，并改善其胰岛素释放功能而不引起肿瘤。在这项研究中，我们研究了PHLDA3缺陷胰岛在移植中的潜在用途。我们注意到：1）将PHLDA3缺陷型胰岛移植到糖尿病小鼠中显著改善了它们的糖代谢状况，2）PHLDA3缺陷型胰岛的植入改善是由于早期移植期间增加的细胞存活，以及3）Akt活性在PHLDA3缺陷型胰岛中升高，特别是在缺氧条件下。因此，我们确定PHLDA3缺陷型胰岛对胰岛分离和移植诱导的应激更具抵抗力。我们的结论是，使用抑制PHLDA3表达的胰岛可能是一种新的和有前途的治疗方法，用于改善胰岛移植的植入和随后的血糖控制。
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.
登录
查看更多内容
影响因子：
8.2
作者：
Liu, Y.;Tanabe, K.;Baronnier, D.;Patel, S.;Woodgett, J.;Cras-Meneur, C.;Permutt, M. A.
通讯作者：
Permutt, M. A.
影响因子：
16.2
作者：
Fiorina, P;La Rosa, S;Secchi, A
通讯作者：
Secchi, A
影响因子：
2.9
作者：
Sakata, Naoaki;Gu, Yuanjun;Inoue, Kazutomo
通讯作者：
Inoue, Kazutomo
影响因子：
0.9
作者：
Stiegler, P.;Schaffellner, S.;Stadlbauer, V.
通讯作者：
Stadlbauer, V.
DOI：
10.1073/pnas.1114228108
发表时间：
2011-10-11
影响因子：
11.1
作者：
Van de Velde, Sam;Hogan, Meghan F.;Montminy, Marc
通讯作者：
Montminy, Marc