Alternative splicing as a novel pathogenic mechanism in chronic kidney disease

Area of Science:

• Nephrology
• Molecular Biology
• Genetics

Background:

• Chronic kidney disease (CKD) affects over 10% of the global population, with incompletely understood pathogenesis hindering effective treatments.
• The balance of damage and repair in renal tubular epithelial cells is critical in CKD progression, with excessive damage leading to fibrosis.
• Alternative splicing (AS) is emerging as a novel pathogenic mechanism in CKD, particularly within renal tubular epithelial cells.

Purpose of the Study:

• To review the regulatory mechanisms of AS in the context of CKD.
• To elucidate the documented and emerging roles of AS in CKD pathogenesis.
• To highlight AS-targeting strategies as potential therapeutic approaches for CKD.

Main Methods:

• Review of recent studies utilizing single-cell sequencing to identify disease-associated dynamics in renal tubular epithelial cells.
• Analysis of literature on the regulatory mechanisms of AS and its role in CKD.
• Examination of the link between gene mutations, abnormal splicing, and familial kidney diseases.

Main Results:

• CKD driver molecules can globally regulate AS, impacting gene expression.
• Key CKD marker genes generate functionally distinct splice isoforms.
• Gene mutations causing abnormal splicing are implicated in the pathogenesis of familial kidney diseases.

Conclusions:

• AS represents a significant pathogenic mechanism in CKD, influencing disease progression.
• Understanding the functional link between AS and CKD is crucial for developing new therapies.
• Targeting AS pathways presents a promising therapeutic strategy for chronic kidney disease.