Global transcriptomic changes occur in aged mouse podocytes
| Autor: | Abbal Koirala, Natalya V. Kaverina, Jeffrey W. Pippin, Shreeram Akilesh, Diana G. Eng, Carol Loretz, Yuliang Wang, Stuart J. Shankland |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Senescence Aging Candidate gene Kidney Glomerulus 030232 urology & nephrology Biology Article Podocyte Transcriptome Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Animals Humans Gene silencing Autocrine signalling Transcription factor Podocytes Cell biology 030104 developmental biology medicine.anatomical_structure Nephrology Kidney Diseases Signal Transduction |
| Zdroj: | Kidney Int |
| ISSN: | 0085-2538 |
| DOI: | 10.1016/j.kint.2020.05.052 |
| Popis: | Glomerular podocytes undergo structural and functional changes with advanced age, that increase susceptibility of aging kidneys to worse outcomes following superimposed glomerular diseases. To delineate transcriptional changes in podocytes in aged mice, RNA-seq was performed on isolated populations of reporter-labeled (tdTomato) podocytes from multiple young (two to three months) and advanced aged mice (22 to 24 months, equivalent to 70 plus year old humans). Of the 2,494 differentially expressed genes, 1,219 were higher and 1,275 were lower in aged podocytes. Pathway enrichment showed that major biological processes increased in aged podocytes included immune responses, non-coding RNA metabolism, gene silencing and MAP kinase signaling. Conversely, aged podocytes showed downregulation of developmental, morphogenesis and metabolic processes. Canonical podocyte marker gene expression decreased in aged podocytes, with increases in apoptotic and senescence genes providing a mechanism for the progressive loss of podocytes seen with aging. In addition, we revealed aberrations in the podocyte autocrine signaling network, identified the top transcription factors perturbed in aged podocytes, and uncovered candidate gene modulations that might promote healthy aging in podocytes. The transcriptional signature of aging is distinct from other kidney diseases. Thus, our study provides insights into biomarker discovery and molecular targeting of the aging process itself within podocytes. |
| Databáze: | OpenAIRE |
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