Research Paper Volume 10, Issue 12 pp 3881—3896
Accelerated aging induced by deficiency of Zmpste24 protects old mice to develop bleomycin-induced pulmonary fibrosis
- 1 Facultad de Ciencias Universidad Nacional Autonoma de México, Mexico City, Mexico
- 2 Cátedra Consejo Nacional de Ciencia y Tecnologia (CONACyT)-INER, Mexico City, Mexico
- 3 Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City, Mexico
- 4 Instituto Nacional de Medicina Genómica, Mexico City, Mexico
received: August 19, 2018 ; accepted: November 18, 2018 ; published: December 10, 2018 ;https://doi.org/10.18632/aging.101679
How to Cite
Copyright: Calyeca et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Idiopathic pulmonary fibrosis is a devastating aging-associated disease of unknown etiology. Despite that aging is a major risk factor, the mechanisms linking aging with this disease are uncertain, and experimental models to explore them in lung fibrosis are scanty. We examined the fibrotic response to bleomycin-induced lung injury in Zmpste24-deficient mice, which exhibit nuclear lamina defects developing accelerated aging. We found that young WT and Zmpste24(-/-) mice developed a similar fibrotic response to bleomycin. Unexpectedly, while old WT mice developed severe lung fibrosis, accelerated aged Zmpste24-/- mice were protected showing scant lung damage. To investigate possible mechanisms associated with this resistance to fibrosis, we compared the transcriptome signature of the lungs and found that Zmpste24(-/-) mice showed downregulation of several core and associated matrisome genes compared with WT mice. Interestingly, some microRNAs that target extracellular matrix molecules such as miR23a, miR27a, miR29a, miR29b-1, miR145a, and miR491 were dysregulated resulting in downregulation of profibrotic pathways such as TGF-β/SMAD3/NF-κB and Wnt3a/β-catenin signaling axis. These results indicate that the absence of Zmpste24 in aging mice results in impaired lung fibrotic response after injury, which is likely associated to the dysregulation of fibrosis-related miRNAs.