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Employing Multi-Omics Analyses to Understand Changes during Kidney Development in Perinatal Interleukin-6 Animal

Ganesh Panzade¹, Tarak Srivastava^2,3, Daniel P Heruth⁴

¹Christopher S. Bond Life Sciences Center, University of Missouri-Columbia, Columbia, MO 65211, USA.

|October 15, 2024

Summary

Maternal inflammation during pregnancy, specifically elevated interleukin-6 (IL-6), alters fetal kidney gene expression. This epigenetic and miRNA dysregulation may program offspring for chronic kidney disease (CKD).

Keywords:

chronic kidney disease (CKD)co-expression epigenetics interleukin-6 (IL-6)miRNA regulation multi-omics

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Area of Science:

Developmental Biology
Genomics
Molecular Biology

Background:

Chronic kidney disease (CKD) is a major global health concern.
Maternal obesity and inflammation, marked by elevated interleukin-6 (IL-6), are linked to adverse intrauterine development.
Previous studies showed maternal IL-6 impacts fetal development in mice.

Purpose of the Study:

To investigate how IL-6-induced maternal inflammation affects fetal kidney gene expression and epigenetic modifications.
To identify key genes and regulatory pathways disrupted by gestational inflammation.

Main Methods:

Pregnant mice were exposed to IL-6 or saline during mid-gestation.
Newborn mouse kidneys were analyzed using multi-omics: mRNA-seq, miRNA-seq, and whole-genome bisulfite sequencing (WGBS).
Bioinformatics and data integration identified key genes regulated by epigenetics and miRNAs.

Main Results:

A multi-omics approach identified 19 key genes regulated by DNA methylation and microRNAs (miRNAs).
Disruptions were observed in pathways including O-glycan biosynthesis, cell cycle, apoptosis, and FoxO signaling.
Specific genes like Atp7b and Man2a1 showed altered regulation via DNA methylation and miRNA targeting.

Conclusions:

Gestational inflammation mediated by IL-6 can induce epigenetic and miRNA changes in the developing fetal kidney.
These molecular alterations in key genes may contribute to fetal programming for later-life diseases, including CKD.