Effect of lung pericyte-like cell ablation on the bleomycin model of injury and repair.
Effect of lung pericyte-like cell ablation on the bleomycin model of injury and repair.
复制标题
DOI：
10.1152/ajplung.00392.2021
复制
发表时间：
2022-04-01
期刊：
影响因子：
--
通讯作者：
Schnapp LM
中科院分区：
文献类型：
--
作者：
Hung CF;Wilson CL;Chow YH;Liles WC;Gharib SA;Altemeier WA;Schnapp LM
我们之前的研究表明，在博莱霉素诱导的肺损伤后，来源于FoxD1系的周细胞样细胞有助于肌成纤维细胞的形成。然而，它们在肺纤维化中的功能意义仍不清楚。在这项研究中，我们使用肺周细胞样细胞消融模型来检验博莱霉素诱导的肺损伤中肺周细胞样细胞消融减轻肺纤维化的假说。气管内滴注博莱霉素诱导肺纤维化。为了去除肺中周细胞样细胞，对Foxd1-Cre；rosa26-iDTR小鼠在博莱霉素性肺损伤的两个不同阶段给予白喉毒素(DT)。为了早期消融，我们在第7天和第21天同时给予博莱霉素和DT，并收获小鼠。为了测试急性损伤后的消融效果，我们在给药后7天交付了DT。通过肺组织羟脯氨酸含量和天狼星红染色半定量分析评价肺纤维化程度。我们进行了支气管肺泡灌洗，以确定细胞计数和细胞分化。我们还询问了全肺RNA中纤维化相关基因的mRNA表达。与周细胞样细胞没有被去除的DT不敏感的小鼠相比，DT敏感的动物在第21天的纤维化方面没有显示出差异，无论是在早期和晚期周细胞消融模型中。然而，如炎症细胞减少所示，早期去除周细胞可减少急性肺炎症。我们的数据证实了周细胞在早期肺损伤中调节肺部炎症的作用。
We previously showed that pericyte-like cells derived from the FoxD1-lineage contribute to myofibroblasts following bleomycin-induced lung injury. However, their functional significance in lung fibrosis remains unknown. In this study, we used a model of lung pericyte-like cell ablation to test the hypothesis that pericyte-like cell ablation attenuates lung fibrosis in bleomycin-induced lung injury. Lung fibrosis was induced by intratracheal instillation of bleomycin. To ablate pericyte-like cells in the lung, diphtheria toxin (DT) was administered to Foxd1-Cre;Rosa26-iDTR mice at two different phases of bleomycin-induced lung injury. For early ablation, we coadministered bleomycin with DT and harvested mice at days 7 and 21. To test the effect of ablation after acute injury, we delivered DT 7 days after bleomycin administration. We assessed fibrosis by lung hydroxyproline content and semiquantitative analysis of picrosirius red staining. We performed bronchoalveolar lavage to determine cell count and differential. We also interrogated mRNA expression of fibrosis-related genes in whole lung RNA. Compared with DT-insensitive littermates where pericyte-like cells were not ablated, DT-sensitive animals exhibited no difference in fibrosis at day 21 both in the early and late pericyte ablation models. However, early ablation of pericytes reduced acute lung inflammation, as indicated by decreased inflammatory cells. Our data confirm a role for pericytes in regulating pulmonary inflammation in early lung injury.
登录
查看更多内容
影响因子：
2.9
作者：
Wang, Jian Fei;Jiao, Haiyan;Tredget, Edward E.
通讯作者：
Tredget, Edward E.
影响因子：
64.8
作者：
Kuppe C;Ibrahim MM;Kranz J;Zhang X;Ziegler S;Perales-Patón J;Jansen J;Reimer KC;Smith JR;Dobie R;Wilson-Kanamori JR;Halder M;Xu Y;Kabgani N;Kaesler N;Klaus M;Gernhold L;Puelles VG;Huber TB;Boor P;Menzel S;Hoogenboezem RM;Bindels EMJ;Steffens J;Floege J;Schneider RK;Saez-Rodriguez J;Henderson NC;Kramann R
通讯作者：
Kramann R
影响因子：
7.3
作者：
Navarro R;Compte M;Álvarez-Vallina L;Sanz L
通讯作者：
Sanz L
DOI：
10.1096/fj.201903192rr
发表时间：
2021-04
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.8
作者：
Hung CF;Rohani MG;Lee SS;Chen P;Schnapp LM
通讯作者：
Schnapp LM