INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors
INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors
复制标题
DOI：
10.1016/j.bbrc.2013.02.042
复制
发表时间：
2013-03-22
影响因子：
3.1
通讯作者：
Ohnishi, Hirohide
中科院分区：
文献类型：
--
作者：
Mashima, Hirosato;Ohno, Hideki;Ohnishi, Hirohide
胰岛素样肽5（INSL 5）是胰岛素超家族的成员，是RXFP 4的有效激动剂。我们已经表明，INSL 5表达肠内分泌细胞（EEC）沿着结肠直肠与梯度增加向直肠。RXFP 4沿着消化道广泛表达。INSL 5阳性的EECs对嗜铬粒蛋白A（CgA）的免疫反应性很低，可能是结直肠EECs的一个独特标志物。CgA阳性内皮细胞在INSL 5缺失小鼠中沿着结直肠正常分布，表明INSL 5不是CgA阳性内皮细胞发育所必需的。外源性INSL 5不影响人结肠癌细胞系的增殖，并且与野生型小鼠相比，INSL 5缺失小鼠中化学诱导的结肠炎在炎症或粘膜愈合方面没有显示出任何显著变化。相反，所有检查的直肠神经内分泌肿瘤均共表达INSL 5和RXFP 4。INSL 5可能是结直肠EC的独特标志物，并且INSL 5 RXFP 4信号传导可能以自分泌/旁分泌方式在结直肠上皮和直肠神经内分泌肿瘤中发挥作用。(C)2013 Elsevier Inc. All rights reserved.
Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosa] healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5 RXFP4 signaling might play a role in an autocrine/ paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors. (C) 2013 Elsevier Inc. All rights reserved.