Affiliation:
1. Infectious Diseases Translational Research Program, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine National University of Singapore Singapore
2. Department of Medicine National University of Singapore Singapore
3. Department of Pathology National University of Singapore Singapore
4. Institute of Molecular and Cell Biology Singapore
5. Adichunchanagiri Institute of Medical Sciences Adichunchanagiri University Karnataka India
6. Department of Medicine University of Cambridge Cambridge UK
Abstract
AbstractIn a mouse model of influenza pneumonia, we previously documented that proliferating alveolar type II (AT2) cells are the major stem cells involved in early lung recovery. Profiling of microRNAs revealed significant dysregulation of specific ones, including miR‐21 and miR‐99a. Moreover, miR‐145 is known to exhibit antagonism to miR‐21. This follow‐up study investigated the roles of microRNAs miR‐21, miR‐99a, and miR‐145 in the murine pulmonary regenerative process and inflammation during influenza pneumonia. Inhibition of miR‐21 resulted in severe morbidity, and in significantly decreased proliferating AT2 cells due to impaired transition from innate to adaptive immune responses. Knockdown of miR‐99a culminated in moderate morbidity, with a significant increase in proliferating AT2 cells that may be linked to PTEN downregulation. In contrast, miR‐145 antagonism did not impact morbidity nor the proliferating AT2 cell population, and was associated with downregulation of TNF‐alpha, IL1‐beta, YM1, and LY6G. Hence, a complex interplay exists between expression of specific miRNAs, lung regeneration, and inflammation during recovery from influenza pneumonia. Inhibition of miR‐21 and miR‐99a (but not miR‐145) can lead to deleterious cellular and molecular effects on pulmonary repair and inflammatory processes during influenza pneumonia.
Funder
National University of Singapore
Ministry of Education - Singapore
Subject
Infectious Diseases,Virology
Cited by
1 articles.
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