ID3 contributes to the acquisition of molecular stem cell-like signature in microvascular endothelial cells: its implication for understanding microvascular diseases.
ID3 contributes to the acquisition of molecular stem cell-like signature in microvascular endothelial cells: its implication for understanding microvascular diseases.
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DOI：
10.1016/j.mvr.2015.01.006
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发表时间：
2015-03
影响因子：
3.1
通讯作者：
Felty, Quentin
中科院分区：
文献类型：
--
作者：
Das, Jayanta K.;Voelkel, Norbert F.;Felty, Quentin
虽然已经取得了重大进展，以推进我们的知识微血管病变的形成，但干细胞样细胞如何可能有助于微血管疾病的发病机制的调查仍处于起步阶段。我们评估了DNA结合和分化抑制剂3（ID 3）是否有助于微血管内皮细胞获得分子干细胞样特征。通过流式细胞术、免疫印迹和免疫组织化学测定了稳定的ID 3过表达和SU 5416处理（微血管病变的化学诱导剂）对干性特征的影响。连续ID 3表达产生由CD 133 + VEGFR 3 + CD 34+细胞组成的分子干性特征。暴露于SU 5416的细胞显示ID 3、VEGFR 3、CD 34蛋白表达阳性，多能转录因子Oct-4和Sox-2表达增加。ID 3过表达细胞支持与平滑肌细胞共培养的3-D微血管病变的形成。此外，来自SuHx啮齿动物模型的体内微血管病变显示与SU 5416处理的人内皮细胞相似的ID 3、VEGFR 3和Pyk 2的表达增加。对正常细胞和干细胞样细胞如何利用ID 3的进一步研究可能为更好地理解微血管疾病病理发展的分子机制开辟新的途径。
While significant progress has been made to advance our knowledge of microvascular lesion formation, yet the investigation of how stem-like cells may contribute to the pathogenesis of microvascular diseases is still in its infancy. We assessed whether the inhibitor of DNA binding and differentiation 3 (ID3) contributes to the acquisition of a molecular stem cell-like signature in microvascular endothelial cells. The effects of stable ID3 overexpression and SU5416 treatment — a chemical inducer of microvascular lesions, had on the stemness signature was determined by flow cytometry, immunoblot, and immunohistochemistry. Continuous ID3 expression produced a molecular stemness signature consisting of CD133+ VEGFR3+ CD34+ cells. Cells exposed to SU5416 showed positive protein expression of ID3, VEGFR3, CD34 and increased expression of pluripotent transcription factors Oct-4 and Sox-2. ID3 overexpressing cells supported the formation of a 3-D microvascular lesion co-cultured with smooth muscle cells. In addition, in vivo microvascular lesions from SuHx rodent model showed an increased expression of ID3, VEGFR3, and Pyk2 similar to SU5416 treated human endothelial cells. Further investigations into how normal and stem-like cells utilize ID3 may open up new avenues for a better understanding of the molecular mechanisms which are underlying the pathological development of microvascular diseases.
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影响因子：
2.6
作者：
Nicolls MR;Mizuno S;Taraseviciene-Stewart L;Farkas L;Drake JI;Al Husseini A;Gomez-Arroyo JG;Voelkel NF;Bogaard HJ
通讯作者：
Bogaard HJ
DOI：
10.1152/ajpregu.00866.2009
发表时间：
2010-12-01
影响因子：
2.8
作者：
Lowery, Jonathan W.;Frump, Andrea L.;de Caestecker, Mark P.
通讯作者：
de Caestecker, Mark P.
DOI：
10.1164/rccm.200709-1369pp
发表时间：
2008-09-15
影响因子：
24.7
作者：
Rai, Pradeep R.;Cool, Carlyne D.;Voelkel, Norbert F.
通讯作者：
Voelkel, Norbert F.
影响因子：
4.1
作者：
Rojiani, AM;DoroviniZis, K
通讯作者：
DoroviniZis, K
影响因子：
4.8
作者：
Taraseviciene-Stewart, L;Kasahara, Y;Tuder, RM
通讯作者：
Tuder, RM