miR-145 transgenic mice develop cardiopulmonary complications leading to postnatal death.
miR-145 transgenic mice develop cardiopulmonary complications leading to postnatal death.
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DOI：
10.14814/phy2.15013
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发表时间：
2021-09
影响因子：
2.5
通讯作者：
Lilly B
中科院分区：
文献类型：
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作者：
Thomas S;Manivannan S;Sawant D;Kodigepalli KM;Garg V;Conway SJ;Lilly B
microRNA miR-145 的下调和升高均与一系列心肺表型有关，大量研究表明它是控制心脏和血管平滑肌细胞类型分化的重要因素。为了更好地了解子宫内升高的 miR-145 在心肺系统中的作用，我们利用转基因在小鼠胚胎中过度表达 miR-145，并检查了这种谱系限制性增强表达的后果。 miR-145 的过度表达会产生有害影响，这种影响在出生后就会显现出来，因为过度表达的小鼠无法在出生后第 18 天后存活。表达 miR-145 的小鼠表现出呼吸窘迫并且无法生长。大体分析显示右心室增大，肺发育不良伴血管肥大。对对照小鼠和 miR-145 转基因小鼠肺部的 RNA 进行单细胞测序表明，miR-145 过度表达对肺部产生整体影响，导致免疫细胞增加，并有证据表明白细胞外渗与血管炎症相关。这些数据提供了新的发现，证明 miR-145 在心肺系统中的病理作用超出了其控制平滑肌分化的正常功能。
Both downregulation and elevation of microRNA miR‐145 has been linked to an array of cardiopulmonary phenotypes, and a host of studies suggest that it is an important contributor in governing the differentiation of cardiac and vascular smooth muscle cell types. To better understand the role of elevated miR‐145 in utero within the cardiopulmonary system, we utilized a transgene to overexpress miR‐145 embryonically in mice and examined the consequences of this lineage‐restricted enhanced expression. Overexpression of miR‐145 has detrimental effects that manifest after birth as overexpressor mice are unable to survive beyond postnatal day 18. The miR‐145 expressing mice exhibit respiratory distress and fail to thrive. Gross analysis revealed an enlarged right ventricle, and pulmonary dysplasia with vascular hypertrophy. Single cell sequencing of RNA derived from lungs of control and miR‐145 transgenic mice demonstrated that miR‐145 overexpression had global effects on the lung with an increase in immune cells and evidence of leukocyte extravasation associated with vascular inflammation. These data provide novel findings that demonstrate a pathological role for miR‐145 in the cardiopulmonary system that extends beyond its normal function in governing smooth muscle differentiation.
DOI：
10.1002/dvg.23385
发表时间：
2020-09
期刊：
Genesis (New York, N.Y. : 2000)
影响因子：
--
作者：
Sawant D;Klevenow E;Baeten JT;Thomas S;Manivannan S;Conway SJ;Lilly B
通讯作者：
Lilly B