Hypoxia and fibrosis in chronic kidney disease: crossing at pericytes.

Chronic kidney disease (CKD) is placing an increasing burden on patients and societies because no decisive therapy has been established. Tubulointerstitial lesions accompanied by fibrosis, inflammatory cells, and capillary rarefaction not only characterize, but also aggravate renal dysfunction in CKD. In this setting, renal cells, particularly tubular cells, suffer from hypoxia caused by the imbalance of blood perfusion and oxygen demand despite their adaptive responses represented by upregulation of hypoxia-inducible factors (HIFs).

Activation of hypoxia-inducible factors prevents diabetic nephropathy.

Hyperglycemia results in increased oxygen consumption and decreased oxygen tension in the kidney. We tested the hypothesis that activation of hypoxia-inducible factors (HIFs) protects against diabetes-induced alterations in oxygen metabolism and kidney function. Experimental groups consisted of control and streptozotocin-induced diabetic rats treated with or without chronic cobalt chloride to activate HIFs.

A multicenter cross-sectional study of circulating soluble urokinase receptor in Japanese patients with glomerular disease.

Elevated serum-soluble urokinase receptor (suPAR) levels have been described in patients with focal segmental glomerulosclerosis (FSGS) in several different cohorts. However, it remains unclear whether this is the case for Japanese patients and whether circulating suPAR can be clinically useful as a diagnostic marker. To determine this, we measured serum suPAR levels in 69 Japanese patients with biopsy-proven glomerular diseases in a cross-sectional manner.

Role of hypoxia in progressive chronic kidney disease and implications for therapy.

Purpose Of Review: Chronic hypoxia in the tubulointerstitium has been recognized as a final common pathway that leads to the development of end-stage renal disease. Hypoxia-inducible factor (HIF), a master regulator of the adaptive response against hypoxia, is involved in the pathogenesis of chronic kidney disease (CKD). This review focuses on HIF and novel therapeutic strategies targeting HIF.

Sperm-associated antigen 4, a novel hypoxia-inducible factor 1 target, regulates cytokinesis, and its expression correlates with the prognosis of renal cell carcinoma.

Hypoxia plays a crucial role in many pathophysiological conditions, including cancer biology, and hypoxia-inducible factor (HIF) regulates transcriptional responses under hypoxia. To elucidate the cellular responses to hypoxia, we performed chromatin immunoprecipitation with deep sequencing in combination with microarray analysis and identified HIF-1 targets. We focused on one of the novel targets, sperm-associated antigen 4 (SPAG4), whose function was unknown.

Anthracycline inhibits recruitment of hypoxia-inducible transcription factors and suppresses tumor cell migration and cardiac angiogenic response in the host.

Anthracycline chemotherapeutic agents of the topoisomerase inhibitor family are widely used for the treatment of various tumors. Although targeted tumor tissues are generally situated in a hypoxic environment, the connection between efficacy of anthracycline agents and cellular hypoxia response has not been investigated in depth. Here, we report that doxorubicin (DXR) impairs the transcriptional response of the hypoxia-inducible factor (HIF) by inhibiting the binding of the HIF heterodimer to the consensus -RCGTG- enhancer element.