# Transcriptome Analysis of BAFF/BAFF-R System in Murine Nephrotoxic Serum Nephritis

## TL;DR

This study explores how the BAFF/BAFF-R system affects kidney disease progression in mice, finding that blocking BAFF may help reduce chronic kidney damage.

## Contribution

The study identifies specific genes influenced by BAFF signaling in CKD and suggests anti-BAFF drugs like belimumab could be a new treatment approach.

## Key findings

- BAFF signaling is directly linked to collagen III upregulation in kidney disease.
- BAFF knockout mice showed reduced collagen III expression, but not via BAFF-R.
- Genes like Txnip, Gpx3, and Igfbp7 are upregulated in chronic kidney injury due to BAFF.

## Abstract

Chronic kidney disease (CKD) is an emerging cause for morbidity and mortality worldwide. Acute kidney injury (AKI) can transition to CKD and finally to end-stage renal disease (ESRD). Targeted treatment is still unavailable. NF-κB signaling is associated with CKD and activated by B cell activating factor (BAFF) via BAFF-R binding. In turn, renal tubular epithelial cells (TECs) are critical for the progression of fibrosis and producing BAFF. Therefore, the direct involvement of the BAFF/BAFF-R system to the pathogenesis of CKD is conceivable. We performed non-accelerated nephrotoxic serum nephritis (NTN) as the CKD model in BAFF KO (B6.129S2-Tnfsf13btm1Msc/J), BAFF-R KO (B6(Cg)-Tnfrsf13ctm1Mass/J) and wildtype (C57BL/6J) mice to analyze the BAFF/BAFF-R system in anti-glomerular basement membrane (GBM) disease using high throughput RNA sequencing. We found that BAFF signaling is directly involved in the upregulation of collagen III as BAFF ko mice showed a reduced expression. However, these effects were not mediated via BAFF-R. We identified several upregulated genes that could explain the effects of BAFF in chronic kidney injury such as Txnip, Gpx3, Igfbp7, Ccn2, Kap, Umod and Ren1. Thus, we conclude that targeted treatment with anti-BAFF drugs such as belimumab may reduce chronic kidney damage. Furthermore, upregulated genes may be useful prognostic CKD biomarkers.