Enhanced Expression of the Female-Biased Gene Gsta2 in Male Proximal Tubule Cells Improves Renal Resilience to Ischemia-Reperfusion Injury.

Background: Genetic sex is an important determinant of kidney injury and repair, with female kidneys typically exhibiting greater resilience to acute kidney injury (AKI). Among the sexually dimorphic genes in mouse proximal tubule cells, Gsta2, encoding an NRF2-regulated antioxidant enzyme, is strongly enriched in females. Here, we hypothesized that augmenting Gsta2 expression in male proximal tubule cells will enhance resistance to ischemia-reperfusion injury (IRI).

Nfkb1 Removal from Proximal Tubule Cells Improves Renal Tubular Outcomes Following Ischemia Reperfusion Injury.

Key Points: Persistent NF-κB signaling associates within injured proximal tubule cells (PTCs) that fail to repair on kidney injury. Removing activity of Nfkb1, a transcriptional effector of NF-κB signaling, in PTCs enhances PTC repair and decreases injury associated fibrosis. Coexpression of and Relb in injured PTCs suggests additional improvement from comprehensive targeting of NF-κB transcriptional regulators.

A scalable organoid model of human autosomal dominant polycystic kidney disease for disease mechanism and drug discovery.

Human pluripotent stem-cell-derived organoids are models for human development and disease. We report a modified human kidney organoid system that generates thousands of similar organoids, each consisting of 1-2 nephron-like structures. Single-cell transcriptomic profiling and immunofluorescence validation highlighted patterned nephron-like structures utilizing similar pathways, with distinct morphogenesis, to human nephrogenesis.

Losartan reduces ensuing chronic kidney disease and mortality after acute kidney injury.

Acute kidney injury (AKI) is an important risk factor for incident chronic kidney disease (CKD). Clinical studies disclose that ensuing CKD progresses after functional recovery from AKI, but the underlying mechanisms remain illusive. Using a murine model representing AKI-CKD continuum, we show angiotensin II type 1a (AT1a) receptor signaling as one of the underlying mechanisms.