original research
Respirometry in intact kidney slices
Congratulations to Ryoichi Bessho on the acceptance of his manuscript in AJP Renal.
October 2025
Regional metabolic analysis of structurally preserved kidney slices by ex vivo respirometry
original research
Mitochondrial electron transport regulates aquaporin-2
Congratulations to Josh Carty, Ryoichi Bessho and team on the acceptance of their manuscript in JCI Insight. In this exciting collaborative study between the Arroyo and Haase labs, we examine the role of oxidative phosphorylation in the regulation of body water homeostasis.
October 2024
Disruption of mitochondrial electron transport impairs urinary concentration via AMPK-dependent suppression of aquaporin-2
original research
Erythropoietic effects of vadadustat in phase 3 trials
Congrats to Mark Koury and colleagues. This study investigates the effects of vadadustat on erythropoiesis and iron metabolism
Jun 2022
Erythropoietic effects of vadadustat in patients with anemia associated with chronic kidney disease
Patients with chronic kidney disease develop anemia largely because of inappropriately low erythropoietin production and insufficient iron available to erythroid precursors. In four phase 3, randomized, open-label, clinical trials in dialysis-dependent and non−dialysis-dependent patients with chronic kidney disease and anemia, the hypoxia-inducible factor prolyl hydroxylase inhibitor, vadadustat, was non-inferior to the erythropoiesis-stimulating agent, darbepoetin alfa, in increasing and maintaining target hemoglobin concentrations. In these trials, vadadustat increased the concentrations of serum erythropoietin, the numbers of circulating erythrocytes, and the numbers of circulating reticulocytes. > …
original research
HIF activation prevents bladder injury
This study from our lab demonstrates that HIF-activating compounds protect from cystitis
May 2022
Inhibition of hypoxia-inducible factor-prolyl hydroxylation protects from cyclophosphamide-induced bladder injury and urinary dysfunction
Disruption of the blood-urine barrier can result in acute or chronic inflammatory bladder injury. Activation of the oxygen-regulated hypoxia-inducible factor (HIF) pathway has been shown to protect mucosal membranes by increasing the expression of cytoprotective genes and by suppressing inflammation. The activity of HIF is controlled by prolyl hydroxylase domain (PHD) dioxygenases, which have been exploited as therapeutic targets for the treatment of anemia of chronic kidney disease. Here we established a mouse model of acute cyclophosphamide (CYP)-induced blood-urine barrier disruption associated with inflammation and severe urinary dysfunction to investigate the HIF-PHD axis in inflammatory bladder injury. We found that systemic administration of dimethyloxalylglycine (DMOG) or molidustat, two small molecule inhibitors of HIF-prolyl hydroxylases (HIF-PHIs), profoundly mitigated CYP-induced bladder injury and inflammation as assessed by morphologic analysis of transmural edema and urothelial integrity and by measuring tissue cytokine expression. > …
original research
Kidney EPO production in CKD is limited by myofibroblast transdifferentiation
This study from our lab demonstrates that HIF-PHIs do not stimulate EPO production in myofibroblasts
May 2022
EPO synthesis induced by HIF-PHD inhibition is dependent on myofibroblast transdifferentiation and colocalizes with non-injured nephron segments in murine kidney fibrosis
Erythropoietin (EPO) is regulated by hypoxia-inducible factor (HIF)-2. In the kidney, it is produced by cortico-medullary perivascular interstitial cells, which transdifferentiate into collagen-producing myofibroblasts in response to injury. Inhibitors of prolyl hydroxylase domain (PHD) dioxygenases (HIF-PHIs) activate HIF-2 and stimulate kidney and liver EPO synthesis in patients with anemia of chronic kidney disease (CKD). We examined whether HIF-PHIs can reactivate EPO synthesis in interstitial cells that have undergone myofibroblast transdifferentiation in established kidney fibrosis. > …
see commentary: The prolyl hydroxylase inhibitor molidustat fails to restore erythropoietin production in the fibrotic kidney [Acta Physiologica 2022].
original research
Mitochondrial electron transport in renal development
This study from our lab identifies a differential role for mitochondrial electron transport in renal progenitors
March 2022
Disruption of mitochondrial complex III in cap mesenchyme but not in ureteric progenitors results in defective nephrogenesis associated with amino acid deficiency.
Oxidative metabolism in mitochondria regulates cellular differentiation and gene expression through intermediary metabolites and reactive oxygen species. Its role in kidney development and pathogenesis is not completely understood. Here we inactivated ubiquinone-binding protein QPC, a subunit of mitochondrial complex III, in two types of kidney progenitor cells to investigate the role of mitochondrial electron transport in kidney homeostasis. Inactivation of QPC in sine oculis-related homeobox 2 (SIX2)-expressing cap mesenchyme progenitors, which give rise to podocytes and all nephron segments except collecting ducts, resulted in perinatal death from severe kidney dysplasia. > …