RNA-Seq analysis reveals critical transcriptome changes caused by sodium butyrate in DN mouse models

Area of Science:

• Nephrology and Endocrinology
• Molecular Biology and Genomics
• Metabolomics and Gut Microbiome Research

Background:

• Diabetic nephropathy (DN) is a leading cause of end-stage renal disease.
• Sodium butyrate (NaB), a short-chain fatty acid (SCFA), shows protective effects in DN, but its mechanism is unclear.
• Understanding NaB's impact on gene expression in DN is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the effect of NaB on the global transcriptome in a mouse model of diabetic nephropathy (DN).
• To identify long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) regulated by NaB in DN.
• To explore the potential mechanisms underlying NaB's renoprotective effects in DN.

Main Methods:

• Utilized a mouse model of DN (db/db mice) treated with NaB or saline.
• Performed whole-transcriptome analysis using RNA sequencing (RNA-Seq) on renal tissues.
• Validated key lncRNA and mRNA expression changes using quantitative real-time polymerase chain reactions (qRT-PCRs).

Main Results:

• NaB treatment ameliorated renal dysfunction in DN mice, evidenced by improved blood glucose, body weight, and urinary markers.
• RNA-Seq identified reversed expression patterns of specific lncRNAs and mRNAs in NaB-treated DN mice compared to controls.
• Integrated co-expression network analysis revealed interactions between NaB-regulated lncRNAs and 155 key mRNAs, particularly those involved in inflammatory responses.

Conclusions:

• Sodium butyrate (NaB) demonstrates a therapeutic effect in ameliorating diabetes-induced renal dysfunction.
• NaB significantly regulates transcriptome changes, including lncRNAs and mRNAs, in the context of diabetic nephropathy.
• The findings suggest that NaB's protective mechanisms involve modulating inflammatory pathways through interactions with specific lncRNAs and mRNAs.