Wingless‐type MMTV integration site family member 5a is a key inhibitor of islet stellate cells activation
Wingless‐type MMTV integration site family member 5a is a key inhibitor of islet stellate cells activation
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Wingless™ 型 MMTV 整合位点家族成员 5a 是胰岛星状细胞激活的关键抑制剂
DOI：
10.1111/jdi.13124
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发表时间：
2019-08
影响因子：
3.2
通讯作者：
Zilin Sun
中科院分区：
文献类型：
--
作者：
Wei Xu;Hou Fa Geng;Jun Liang;Ying Liu;Qian Lv;Jie Wang;Rui Li;Xiuli Wang;Xui Kui Liu;Peter B. Jones;Zilin Sun
2型糖尿病是一种以胰岛β细胞功能障碍为特征的慢性代谢性疾病，其可能是由胰岛星状细胞（ISCs）活化引起的。我们最近的研究表明，在2型糖尿病患者中，一个特定的ISCs群体易于被激活，并伴有胰岛素分泌减少。无翅型MMTV整合位点家族成员5a（Wnt 5a）/frizzled-5信号通路可能在此过程中发挥重要作用。本研究旨在探讨Wnt 5a对db/db小鼠ISCs活化的影响。采用免疫组化和Western blotting方法检测Wnt 5a的表达。使用外源性Wnt 5a和含有靶基因Wnt 5a短发夹核糖核酸的慢病毒作为分子干预。transwell实验和伤口愈合实验检测分离的ISCs迁移能力，结果显示db/db小鼠ISCs中Wnt 5a和frizzled-5的表达较db/m小鼠明显降低。外源性Wnt 5a和过表达Wnt 5a均能抑制胰岛ISCs的生长速度，抑制ISCs的存活、迁移和α平滑肌肌动蛋白的表达。这些变化与Smad 2/3信号通路的失活有关，并以frizzled-5依赖的方式进行。维持静止的ISCs可能是糖尿病治疗策略的理想结果。
Type 2 diabetes mellitus is a chronic metabolic disorder characterized by islet β-cell dysfunction, which might result from the activation of islet stellate cells (ISCs). Our recent study showed that a specific population of ISCs is prone to be activated in type 2 diabetes mellitus accompanied by reduced secretion of insulin. The wingless-type MMTV integration site family member 5a (Wnt5a)/frizzled-5 signaling pathway might play an important role in this process. The present study aimed to explore the effects of Wnt5a on the activation of ISCs isolated from db/db mice.ISCs were isolated from db/db mice and matched db/m mice. Immunohistochemistry and western blotting analysis were applied for the determination of Wnt5a expression. Exogenous Wnt5a and lentivirus containing the target gene Wnt5a short hairpin ribonucleic acid were used as a molecular intervention. The experiment of transwell and wound healing was used to evaluate the migration of the isolated ISCs.Our data showed that the expression of Wnt5a and frizzled-5 was decreased in the ISCs isolated from db/db mice compared with db/m mice. Both the exogenous Wnt5a and the overexpression of Wnt5a could inhibit the outgrowth rate of ISCs from islets, and its viability, migration and α smooth muscle actin expression. These changes were associated with the inactivation of the Smad2/3 signaling pathway in a frizzled-5-dependent manner.Our observations revealed a potential role of Wnt5a in preventing ISC activation. The maintenance of quiescent ISCs might be a desirable outcome of therapeutic strategies for diabetes mellitus.
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影响因子：
2.2
作者：
Kim, Tae Hyung;Kim, Sang-Heon;Sohn, Jang Won
通讯作者：
Sohn, Jang Won
影响因子：
4.3
作者：
Li FF;Chen BJ;Li W;Li L;Zha M;Zhou S;Bachem MG;Sun ZL
通讯作者：
Sun ZL
DOI：
--
发表时间：
1988-12
期刊：
Diabetes research
影响因子：
--
作者：
Anne Clark;C. Wells;I. Buley;J. Cruickshank;R. Vanhegan;David R. Matthews;Garth J. S. Cooper;Rury R. Holman;Robert C. Turner
通讯作者：
Anne Clark;C. Wells;I. Buley;J. Cruickshank;R. Vanhegan;David R. Matthews;Garth J. S. Cooper;Rury R. Holman;Robert C. Turner
DOI：
10.1177/0032885598078003008
发表时间：
1998-09
期刊：
The Prison Journal
影响因子：
--
作者：
Irina Simonovska;I. Mateescu;V. Manolache
通讯作者：
Irina Simonovska;I. Mateescu;V. Manolache
影响因子：
7.7
作者：
Porksen, N;Hollingdal, M;Schmitz, O
通讯作者：
Schmitz, O