Hs3st-A and Hs3st-B regulate intestinal homeostasis in Drosophila adult midgut
Hs3st-A and Hs3st-B regulate intestinal homeostasis in Drosophila adult midgut
复制标题
Hs3st-A 和 Hs3st-B 调节果蝇成年中肠的肠道稳态。
DOI：
10.1016/j.cellsig.2014.07.015
复制
发表时间：
2014-11-01
影响因子：
4.8
通讯作者：
Lin, Xinhua
中科院分区：
文献类型：
--
作者：
Guo, Yueqin;Li, Zhouhua;Lin, Xinhua
内在和外在信号以及细胞外基质（ECM）严格调节干细胞的组织稳态和再生能力。关于 ECM 对组织稳态的调节知之甚少。硫酸乙酰肝素蛋白聚糖 (HSPG) 是 ECM 的重要组成部分，参与多种生物事件。两个硫酸肝素 3-O 磺基转移酶 (Hs3st) 基因 Hs3st-A 和 Hs3st-B 编码硫酸乙酰肝素 (HS) 生物合成中的修饰酶。在这里，我们证明 Hs3st-A 和 Hs3st-B 是成人中肠稳态所必需的。肠上皮细胞 (EC) 中 Hs3st-A 的消耗会导致肠干细胞 (ISC) 增殖增加和组织稳态丧失。此外，在单独的 Hs3st-B 无效突变体或与 Hs3st-A RNAi 组合中也观察到 ISC 增殖增加。同时抑制 EGFR 信号通路可有效抑制 Hs3st-A 耗竭诱导的 ISC 增殖，这表明 Hs3st-A 缺陷肠道中组织稳态丧失是由于 EGFR 信号传导增加所致。此外，我们发现 Hs3st-A 耗尽的 EC 不健康且容易死亡，而抗凋亡 p35 的异位表达能够极大地抑制这些肠道中组织稳态的丧失。总之，我们的数据表明果蝇 Hs3st-A 和 Hs3st-B 参与 ISC 增殖和中肠稳态维持的调节。 (C) 2014 年，爱思唯尔公司出版
Intrinsic and extrinsic signals as well as the extracellular matrix (ECM) tightly regulate stem cells for tissue homeostasis and regenerative capacity. Little is known about the regulation of tissue homeostasis by the ECM. Heparan sulfate proteoglycans (HSPGs), important components of the ECM, are involved in a variety of biological events. Two heparin sulfate 3-O sulfotransferase (Hs3st) genes, Hs3st-A and Hs3st-B, encode the modification enzymes in heparan sulfate (HS) biosynthesis. Here we demonstrate that Hs3st-A and Hs3st-B are required for adult midgut homeostasis. Depletion of Hs3st-A in enterocytes (ECs) results in increased intestinal stem cell (ISC) proliferation and tissue homeostasis loss. Moreover, increased ISC proliferation is also observed in Hs3st-B null mutant alone, or in combination with Hs3st-A RNAi. Hs3st-A depletion-induced ISC proliferation is effectively suppressed by simultaneous inhibition of the EGFR signaling pathway, suggesting that tissue homeostasis loss in Hs3st-A-deficient intestines is due to increased EGFR signaling. Furthermore, we find that Hs3st-A-depleted ECs are unhealthy and prone to death, while ectopic expression of the antiapoptotic p35 is able to greatly suppress tissue homeostasis loss in these intestines. Together, our data suggest that Drosophila Hs3st-A and Hs3st-B are involved in the regulation of ISC proliferation and midgut homeostasis maintenance. (C) 2014 Published by Elsevier Inc.