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Bilateral Renal Ischemia-Reperfusion Model for Acute Kidney Injury in Mice
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Kidney Damage in Long COVID: Studies in Experimental Mice
Rajalakshmi Ramamoorthy1, Hussain Hussain2, Natalia Ravelo1
1Department of Obstetrics, Gynecology and Reproductive Sciences, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Biology
|August 26, 2023
Summary
Long COVID can cause persistent kidney damage. This study in mice suggests fibrotic events may start early in infection, potentially leading to kidney fibrosis. Therapeutic targeting may prevent long COVID kidney complications.
Area of Science:
- Nephrology
- Virology
- Immunology
Background:
- Post-acute sequelae of SARS-CoV-2 infection (PASC), or long COVID, commonly involves multiple organ systems.
- Kidney injury is a recognized complication in COVID-19 patients, supported by findings in animal models.
- Previous studies reported pathophysiological changes in mouse kidneys after acute and long-term infection with mouse hepatitis virus-1 (MHV-1).
Purpose of the Study:
- To investigate the molecular mechanisms underlying kidney pathology in a mouse model of long-term coronavirus infection.
- To identify specific signaling pathways and biomarkers associated with kidney fibrosis post-infection.
- To evaluate the therapeutic potential of targeting viral spike protein interactions.
Main Methods:
- Pathological examination of mouse kidneys at acute (7 days) and long-term (12 months) post-MHV-1 infection.
- Quantitative mRNA analysis of key fibrotic and inflammatory markers.
- Immunoblotting to assess protein level changes.
- In vivo treatment with a synthetic peptide (SPIKENET) inhibiting spike protein binding.
Main Results:
- Long-term MHV-1 infection led to renal parenchyma edema, inflammation, tubular necrosis, and immune cell infiltration.
- Elevated mRNA levels of TGF-β1, FGF23, NGAL, IL-18, HIF1-α, TLR2, YKL-40, and B2M were observed in long-term infection; NGAL was elevated in acute infection.
- Protein analysis revealed increased HIF1-α, TLR-2, and EGFR in long-term infection, while KIM-1 and MMP-7 increased in acute infection.
- SPIKENET treatment reduced NGAL mRNA in acute infection and decreased TGF-β1, BCL3 mRNA, EGFR, HIF1-α, and TLR-2 protein levels in long-term infection.
Conclusions:
- Kidney fibrosis may initiate early during coronavirus infection, contributing to long COVID-associated renal complications.
- Specific molecular markers like NGAL, TGF-β1, and HIF1-α are implicated in the development of kidney fibrosis.
- Targeting viral spike protein interactions with agents like SPIKENET shows promise in mitigating acute and long-term kidney damage.
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