biostudies-literatureHung CFNHLBI NIH HHSHHS | NIH | National Heart, Lung, and Blood InstituteNCI NIH HHSMUSC | Hollings Cancer Center, Medical University of South CarolinaL607-L616https://www.ebi.ac.uk/biostudies/studies/S-EPMC8993536biostudies-literatureUnknown322(4)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 <i>Foxd1-Cre;Rosa26-iDTR</i> mice at two different phases of bleomycin-induced lung injury. For early ablation, we coadministered bleomycin with DT and harvested mice at <i>days 7</i> and <i>21</i>. 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 <i>day 21</i> 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.American journal of physiology. Lung cellular and molecular physiologyEffect of lung pericyte-like cell ablation on the bleomycin model of injury and repair.PMC8993536P30 CA138313R03HL155075-01A1R01 HL133751K08 HL127075R01HL122895R01HL133751R03 HL155075K08HL127075R01 HL122895Schnapp LMHung CFLiles WCWilson CLAltemeier WAGharib SAChow YHfalseEffect of lung pericyte-like cell ablation on the bleomycin model of injury and repair.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 <i>Foxd1-Cre;Rosa26-iDTR</i> mice at two different phases of bleomycin-induced lung injury. For early ablation, we coadministered bleomycin with DT and harvested mice at <i>days 7</i> and <i>21</i>. 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 <i>day 21</i> 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.2022-01-01T00:00:00Z2022 Apr2025-04-04T19:10:16.268Z2024-11-19T21:56:54.62ZS-EPMC89935363519690110.1152/ajplung.00392.2021