Ngn3 expression during postnatal in vitro beta cell neogenesis induced by the JAK/STAT pathway
Ngn3 expression during postnatal in vitro beta cell neogenesis induced by the JAK/STAT pathway
复制标题
DOI：
10.1038/sj.cdd.4401883
复制
发表时间：
2006-11-01
影响因子：
12.4
通讯作者：
Bouwens, L.
中科院分区：
文献类型：
--
作者：
Baeyens, L.;Bonne, S.;Bouwens, L.
碱性螺旋-环-螺旋蛋白Neurogenin 3在胚胎发育期间指定内分泌胰腺的前体细胞，并且被认为在出生后不存在。我们已经研究了Ngn 3的表达过程中，在体外生成的β-细胞从成年大鼠外分泌胰腺组织处理表皮生长因子和白血病抑制因子。这种治疗诱导了Ngn 3及其上游激活剂肝细胞核因子6的瞬时表达。通过JAK 2/STAT 3通路的药理学拮抗剂抑制EGF和LIF信号传导，或通过RNA干扰敲低Ngn 3，阻止了新胰岛素阳性细胞的产生。这项研究表明，在体外生长因子刺激可以诱导重演的胚胎内分泌分化途径在成人去分化外分泌细胞。这对于理解β细胞再生的机制和β细胞的治疗性离体新生可能被证明是重要的。
The basic helix-loop-helix protein Neurogenin3 specifies precursor cells of the endocrine pancreas during embryonic development, and is thought to be absent postnatally. We have studied Ngn3 expression during in vitro generation of beta-cells from adult rat exocrine pancreas tissue treated with epidermal growth factor and leukaemia inhibitory factor. This treatment induced a transient expression of both Ngn3 and its upstream activator hepatocyte nuclear factor 6. Inhibition of EGF and LIF signalling by pharmacological antagonists of the JAK2/STAT3 pathway, or knockdown of Ngn3 by RNA interference prevented the generation of new insulin-positive cells. This study demonstrates that in vitro growth factor stimulation can induce recapitulation of an embryonic endocrine differentiation pathway in adult dedifferentiated exocrine cells. This could prove to be important for understanding the mechanism of beta-cell regeneration and for therapeutic ex vivo neogenesis of beta cells.