Human proximal tubular epithelial cell interleukin-1 receptor signalling triggers G2/M arrest and cellular senescence during hypoxic kidney injury.

ABSTRACT: Hypoxia and interleukin (IL)-1β are independent mediators of tubulointerstitial fibrosis, the histological hallmark of chronic kidney disease (CKD). Here, we examine how hypoxia and IL-1β act in synergy to augment maladaptive proximal tubular epithelial cell (PTEC) repair in human CKD. Ex vivo patient-derived PTECs were cultured under normoxic (21% O₂) or hypoxic (1% O₂) conditions in the absence or presence of IL-1β and examined for maladaptive repair signatures. Hypoxic PTECs incubated with IL-1β displayed a discrete transcriptomic profile distinct from PTECs cultured under hypoxia alone, IL-1β alone or under normoxia. Hypoxia+IL-1β-treated PTECs had 692 'unique' differentially expressed genes (DEGs) compared to normoxic PTECs, with 'cell cycle' the most significant

SUBMITTER: Giuliani KTK 

PROVIDER: S-EPMC11785723 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature