Nfkb1 removal from proximal tubule cells improves renal tubular outcomes following ischemia reperfusion injury
Chronic kidney disease (CKD) is a significant global health burden. Acute kidney injury (AKI) is a risk factor for progression to CKD. Recent studies have linked a failure in proximal tubule repair as a potential contributing factor to CKD in mouse and human studies. Failed repair proximal tubule cells (FR-PTCs), initially present at the site of maximal sensitivity to ischemia reperfusion injury and spreading to more cortical regions over time, adopt a senescence-associated secretory phenotype (SASP) linked to activation of the NF-kB pathway. Several transcriptional regulatory factors mediate NF-kB pathway action. Of these, Nfkb1 is prominent within FR-PTCs and chromatin studies predict Nfkb1 interactions with pathology-associated gene targets. To examine the role of NF-kB in nephron injury outcomes, we removed Nfkb1 activity within the nephron lineage of the mouse kidney and examined the kidney's response to bilateral ischemia reperfusion injury (Bi-IRI). Overall design: In total 7 samples from Six2CreTGC/+;Nfkb1Null/c and Nfkb1c/c  mice were processed for snRNA-seq+snATAC-seq: three mice of Nfkb1c/c  at 4 weeks post-IRI; four mice of Six2CreTGC/+;Nfkb1Null/c at 4 weeks post-IRI.