Sci Rep
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Published: August 2022
Long-term administration of lithium is associated with chronic interstitial fibrosis that is partially reduced with exposure to amiloride. We examined potential pathways of how amiloride may reduce interstitial fibrosis. Amiloride was administered to a rat model of lithium induced interstitial fibrosis over a long term (6 months), as well as for short terms of 14 and 28 days. Kidney cortical tissue was subjected to RNA sequencing and microRNA expression analysis. Gene expression changes of interest were confirmed using immunohistochemistry on kidney tissue. Pathways identified by RNA sequencing of kidney tissue were related to 'promoting inflammation' for lithium and 'reducing inflammation' for amiloride. Validation of candidate genes found amiloride reduced inflammatory components induced by lithium including NF-κB/p65 and activated pAKT, and increased p53 mediated regulatory function through increased p21 in damaged tubular epithelial cells. Amiloride also reduced the amount of Notch1 positive PDGFrβ pericytes and infiltrating CD3 cells in the interstitium. Thus, amiloride attenuates a multitude of pro-inflammatory components induced by lithium. This suggests amiloride could be repurposed as a possible anti-inflammatory, anti-fibrotic agent to prevent or reduce the development of chronic interstitial fibrosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9418221 | PMC |
http://dx.doi.org/10.1038/s41598-022-18825-1 | DOI Listing |
Geroscience
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Buck Institute for Research On Aging, Novato, CA, 94945, USA.
Cells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood.
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View Article and Find Full Text PDFAcad Radiol
January 2025
Department of Radiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310007, Zhejiang Province, China (Y.R., W.L., Y.Z., S.K., F.C.). Electronic address:
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Transl Pediatr
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Department of Pediatric Intensive Care Unit, National Regional Medical Center, Guizhou Branch of Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Guizhou Provincial People's Hospital, Guiyang, China.
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