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A4645 - Absence of Zmpste24 Protects Aging Mice from the Development of Bleomycin Induced Pulmonary Fibrosis Through microRNAs Expression
Author Block: M. J. Calyeca1, R. Olmos2, R. Jasso2, Y. I. Balderas-Martinez3, Q. Rivera1, V. Maldonado4, M. Gaxiola2, M. Selman2, A. Pardo1; 1Facultad de Ciencias, Univ Nacional Autonoma de Mexico, Mexico, Mexico, 2Instituto Nacional de Enfermedades Respiratorias, Mexico, Mexico, 3Catedra CONACYT, Mexico, Mexico, 4Instituto Nacional de Medicina Genomica, Mexico, Mexico.
Rationale: Idiopathic Pulmonary Fibrosis is a progressive and lethal disease of unknown etiology. Strong evidence indicates that aging is a driving force of the disease, and actually, the incidence and prevalence of IPF increases remarkably with age. Notwithstanding, the mechanisms linking IPF to aging are uncertain. Unfortunately, models of lung fibrosis using aged mice are scanty among other problems due to long time and expensive cost of production. In this context, growing evidence suggest that genetically-modified mice that display accelerated aging may be useful to understand some aging-associated mechanisms that may contribute to the development of fibrosis. Methods: We have been examining the lung phenotype and the fibrotic response of the Zmpste24 deficient mice, which show numerous features of accelerated aging, and surprisingly, we have found that these mice develop less fibrosis with aging compared with the wild-type. In this study, we explored some putative mechanisms that may contribute to this observation. Results: At 3 weeks after bleomycin injury, morphological analysis displayed that aged Zmpste24 deficient mice showed less inflammation and fibrosis compared with aged wildtypes counterparts. The attenuation of the fibrotic response was confirmed by a significant decrease in lung hydroxyproline content. Global gene expression analysis revealed an increased expression of several antifibrotic microRNAs including miR23a, miR27a, miR29a and miR29b-1 in bleomycin damaged lungs of Zmpste24 mice, which was validated by qPCR. As expected, several targets of these microRNAs, including collagen, fibronectin were decreased. Conclusions: Our results suggest that the absence of Zmpste24 protects aged mice from the development of bleomycin-induced pulmonary fibrosis by the over-expression of microRNAs with antifibrotic activity.