Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells.
Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells.
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DOI：
10.1038/s41467-020-19657-1
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发表时间：
2020-11-25
影响因子：
16.6
通讯作者：
Gasa R
中科院分区：
文献类型：
--
作者：
Fernandez-Ruiz R;García-Alamán A;Esteban Y;Mir-Coll J;Serra-Navarro B;Fontcuberta-PiSunyer M;Broca C;Armanet M;Wojtusciszyn A;Kram V;Young MF;Vidal J;Gomis R;Gasa R
已经提出通过β细胞复制的再激活来扩大胰腺产生胰岛素的β细胞的质量作为预防或延迟糖尿病的出现的疗法。胰腺β细胞表现出其增殖活性的年龄依赖性降低，部分与全身环境的变化有关。在这里，我们报告的CCN 4/Wisp 1作为一个循环因子更丰富的断奶前比成年小鼠的鉴定。我们表明，Wisp 1促进内源性和移植的成人β细胞在体内增殖。我们使用分离的小鼠和人类胰岛验证了这些发现，并发现Wisp 1的β细胞营养作用依赖于Akt信号传导。总之，我们的研究揭示了Wisp 1作为β细胞复制诱导剂的作用，支持了使用年轻血液因子可能是扩大成人β细胞群的有用策略的观点。胰腺β细胞的增殖随着年龄的增长而减少，部分原因是系统性变化。在这里，作者将Wisp 1确定为富含年轻血清的循环因子，其诱导成人β细胞增殖，支持年轻血液因子可能有助于扩大β细胞群的观点。
Expanding the mass of pancreatic insulin-producing beta cells through re-activation of beta cell replication has been proposed as a therapy to prevent or delay the appearance of diabetes. Pancreatic beta cells exhibit an age-dependent decrease in their proliferative activity, partly related to changes in the systemic environment. Here we report the identification of CCN4/Wisp1 as a circulating factor more abundant in pre-weaning than in adult mice. We show that Wisp1 promotes endogenous and transplanted adult beta cell proliferation in vivo. We validate these findings using isolated mouse and human islets and find that the beta cell trophic effect of Wisp1 is dependent on Akt signaling. In summary, our study reveals the role of Wisp1 as an inducer of beta cell replication, supporting the idea that the use of young blood factors may be a useful strategy to expand adult beta cell mass. The proliferation of pancreatic beta cells decreases with age, partly due to systemic changes. Here the authors identify Wisp1 as a circulating factor enriched in young serum that induces adult beta cell proliferation, supporting the idea that young blood factors may be useful to expand beta cell mass.
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影响因子：
8.2
作者：
Hoerbeit, Tina;Tacke, Christopher;Ouwens, D. Margriet
通讯作者：
Ouwens, D. Margriet
影响因子：
64.8
作者：
Conboy, IM;Conboy, MJ;Rando, TA
通讯作者：
Rando, TA
影响因子：
4.8
作者：
Arafat, Hwyda A.;Katakam, Anand K.;Dafoe, Donald C.
通讯作者：
Dafoe, Donald C.
影响因子：
29
作者：
Kondegowda NG;Fenutria R;Pollack IR;Orthofer M;Garcia-Ocaña A;Penninger JM;Vasavada RC
通讯作者：
Vasavada RC
影响因子：
8.8
作者：
El Ouaamari A;Kawamori D;Dirice E;Liew CW;Shadrach JL;Hu J;Katsuta H;Hollister-Lock J;Qian WJ;Wagers AJ;Kulkarni RN
通讯作者：
Kulkarni RN