Hashemi Gheinani, Ali; Sack, Bryan S; Bigger-Allen, Alex; Thaker, Hatim; Atta, Hussein; Lambrinos, George; Costa, Kyle; Doyle, Claire; Gharaee-Kermani, Mehrnaz; Patalano, Susan; Piper, Mary; Cotellessa, Justin F; Vitko, Dijana; Li, Haiying; Prabhakaran, Manubhai Kadayil; Cristofaro, Vivian; Froehlich, John; Lee, Richard S; Yang, Wei; Sullivan, Maryrose P; ... (10 December 2023). Integrated omics analysis unveils a DNA damage response to neurogenic injury. (bioRxiv). Cold Spring Harbor Laboratory 10.1101/2023.12.10.571015
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2023.12.10.571015v1.full.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND). Download (9MB) | Preview |
Spinal cord injury (SCI) evokes profound bladder dysfunction. Current treatments are limited by a lack of molecular data to inform novel therapeutic avenues. Previously, we showed systemic inosine treatment improved bladder function following SCI in rats. Here, we applied multi-omics analysis to explore molecular alterations in the bladder and their sensitivity to inosine following SCI. Canonical pathways regulated by SCI included those associated with protein synthesis, neuroplasticity, wound healing, and neurotransmitter degradation. Upstream regulator analysis identified MYC as a key regulator, whereas causal network analysis predicted multiple regulators of DNA damage response signaling following injury, including PARP-1. Staining for both DNA damage (γH2AX) and PARP activity (poly-ADP-ribose) markers in the bladder was increased following SCI, and attenuated in inosine-treated tissues. Proteomics analysis suggested that SCI induced changes in protein synthesis-, neuroplasticity-, and oxidative stress-associated pathways, a subset of which were shown in transcriptomics data to be inosine-sensitive. These findings provide novel insights into the molecular landscape of the bladder following SCI, and highlight a potential role for PARP inhibition to treat neurogenic bladder dysfunction.
Item Type: |
Working Paper |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie 04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology |
UniBE Contributor: |
Hashemi Gheinani, Ali |
Subjects: |
600 Technology > 610 Medicine & health |
Series: |
bioRxiv |
Publisher: |
Cold Spring Harbor Laboratory |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
04 Jan 2024 11:56 |
Last Modified: |
04 Jan 2024 12:04 |
Publisher DOI: |
10.1101/2023.12.10.571015 |
PubMed ID: |
38106029 |
Uncontrolled Keywords: |
DNA damage PARP-1 activation neurogenic bladder tissue remodeling |
BORIS DOI: |
10.48350/190774 |
URI: |
https://boris.unibe.ch/id/eprint/190774 |
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