INK4a deletion results in improved kidney regeneration and decreased capillary rarefaction after ischemia-reperfusion injury.

The molecular mechanisms that lead to tubular atrophy, capillary loss, and fibrosis following acute kidney injury are not very clear but may involve cell cycle inhibition by increased expression of cyclin kinase inhibitors. The INK4a/ARF locus encodes overlapping genes for two proteins, a cyclin kinase inhibitor, p16(INK4a), and a p53 stabilizer, p19(ARF), from independent promoters. To determine if decreased INK4a gene expression results in improved kidney regeneration, INK4a knockout (KO) and wild-type (WT) mice were subjected to ischemia-reperfusion injury (IRI).

Biliverdin Rescues the HO-2 Null Mouse Phenotype of Unresolved Chronic Inflammation Following Corneal Epithelial Injury.

PURPOSE. The heme oxygenase system (HO-1 and HO-2) represents an intrinsic cytoprotective and anti-inflammatory pathway based on its ability to modulate leukocyte migration and to inhibit the expression of inflammatory cytokines and proteins by its products biliverdin/bilirubin and carbon monoxide. Corneal injury in HO-2 null mice leads to impaired healing and chronic inflammatory complications, including ulceration and neovascularization.

INK4a knockout mice exhibit increased fibrosis under normal conditions and in response to unilateral ureteral obstruction.

The INK4a proteins p16(INK4a) and p19(ARF) regulate cell cycle arrest and senescence. However, the role of these proteins in controlling these processes in the normal kidney and following injury is unknown. We performed unilateral ureteral obstruction (UUO) to induce fibrosis in 2- to 3-mo-old wild-type (WT) C57/B6 and INK4a knockout mice.