Sex-Related Differences in Murine Models of Chemically Induced Pulmonary Fibrosis.
Sex-Related Differences in Murine Models of Chemically Induced Pulmonary Fibrosis.
复制标题
化学诱导的肺纤维化的鼠模型中的性别相关差异。
DOI：
10.3390/ijms22115909
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发表时间：
2021-05-31
影响因子：
5.6
通讯作者：
Catravas JD
中科院分区：
文献类型：
--
作者：
Solopov P;Colunga Biancatelli RML;Dimitropoulou C;Catravas JD
我们开发了两种化学诱导的小鼠慢性肺损伤和肺纤维化模型（气管内注射盐酸（HCl）和气管内注射氮芥（NM）），并研究了雄性和雌性的差异。雌性小鼠的30天存活率高于雄性小鼠，体重减轻较少。在滴注HCl或NM后30天，支气管肺泡灌洗液显示出持续的轻度炎症反应，但雄性动物的白色血细胞数量和总蛋白含量高于雌性动物。此外，女性表现出较少的胶原蛋白沉积，轻度肺纤维化，和较低的Ashcroft评分。在滴注HCl或NM后，所有动物均显示磷酸化（活化）热休克蛋白90的值增加，其在肺泡伤口愈合过程中起关键作用;然而，雌性动物的转化生长因子-β（TGF-β）信号通路：ERK和SMAD的活化较低。我们认为，雌性小鼠通过较少的TGF-β和下游信号传导的活化而免受单次暴露于HCl或NM的慢性并发症的影响。对赋予女性保护作用的分子机制的理解可以帮助开发新的、性别特异性的IPF治疗方法。
We developed two models of chemically induced chronic lung injury and pulmonary fibrosis in mice (intratracheally administered hydrochloric acid (HCl) and intratracheally administered nitrogen mustard (NM)) and investigated male–female differences. Female mice exhibited higher 30-day survival and less weight loss than male mice. Thirty days after the instillation of either HCl or NM, bronchoalveolar lavage fluid displayed a persistent, mild inflammatory response, but with higher white blood cell numbers and total protein content in males vs. females. Furthermore, females exhibited less collagen deposition, milder pulmonary fibrosis, and lower Ashcroft scores. After instillation of either HCl or NM, all animals displayed increased values of phosphorylated (activated) Heat Shock Protein 90, which plays a crucial role in the alveolar wound-healing processes; however, females presented lower activation of both transforming growth factor-β (TGF-β) signaling pathways: ERK and SMAD. We propose that female mice are protected from chronic complications of a single exposure to either HCl or NM through a lesser activation of TGF-β and downstream signaling. The understanding of the molecular mechanisms that confer a protective effect in females could help develop new, gender-specific therapeutics for IPF.
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影响因子：
3.7
作者：
García-Prieto E;González-López A;Cabrera S;Astudillo A;Gutiérrez-Fernández A;Fanjul-Fernandez M;Batalla-Solís E;Puente XS;Fueyo A;López-Otín C;Albaiceta GM
通讯作者：
Albaiceta GM
DOI：
10.1164/rccm.201403-0509pp
发表时间：
2014-10-15
影响因子：
24.7
作者：
Ahluwalia, Neil;Shea, Barry S.;Tager, Andrew M.
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影响因子：
3.1
作者：
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影响因子：
9.6
作者：
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通讯作者：
BERNSTEIN, IL
DOI：
10.1073/pnas.0809120105
发表时间：
2008-12-16
影响因子：
11.1
作者：
Pergola, Carlo;Dodt, Gabriele;Werz, Oliver
通讯作者：
Werz, Oliver