Loss of Alpha(E)‐Catenin: Potential Role in the Renal Disrepair Following Injury in the Aging Kidney

Abstract

As the kidney ages, morphological and functional changes lead to renal dysfunction. Clinical data indicates decreased ability to repair following acute insult which leads to increased susceptibility and severity of acute kidney injury (AKI). We have previously shown the aging kidney has a marked loss of α‐catenin expression in the proximal tubular epithelium. We hypothesize that the loss of this protein may be involved in the decreased repair of the aging kidney. To study the effects of reduced α‐catenin, shRNA knock‐down of α‐catenin was generated in NRK‐52E cells. Single cell clones were selected for a non‐targeted (NT3) control and a targeted knock‐down (C2). The 75% reduction of α‐catenin mRNA and protein levels was stable over several passages compared to the NT3 control. Interestingly, the catenin knockdown affected expression of other components of the cadherin/catenin complex. Most notably, mRNA expression of N‐cadherin was reduced >;99% and protein was undetectable in C2. This was paralleled by a decrease in cadherin/catenin function as assessed by aggregate formation, as well as inhibition of wound healing as determined by a scratch assay. NextGen RNA sequencing revealed alterations in several genes which are implicated in renal repair, including proliferation/growth factor signaling, and cytoskeletal organization. This work was supported by NIH AG034154.