A team led by researchers at Massachusetts General Hospital (MGH) used
Previously, researchers conducted experiments onanimals and identified various factors involved in kidney recovery. But extrapolating them to humans and making them part of clinical practice has been difficult. Many treatments that were considered safe and effective in animals were later found to be toxic or ineffective in clinical trials. Human kidney organoids that resemble scaled-down real kidneys could help researchers avoid these problems.
The authors of the new work used on an organoidthe chemotherapy drug cisplatin, which can damage the kidneys. The treatment altered the expression of 159 genes and 29 signaling pathways in kidney cells. Many of the genes identified, including two—FA NCD2 and Rad51—were activated during repair, but their expression decreased as the damage became irreversible.
These genes encode proteins that play an important role in DNA repair. Additional experiments in mouse models confirmed the results.
The scientists then used screening tests to identify the SCR7 compound, which helped maintain the activity of the FANCD2 and RAD51 genes.
The authors of the new work said they figured out how to activate the DNA repair mechanism in the kidneys: it will help maintain their performance.
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