腎臓における酸素代謝異常と，新規低酸素治療ターゲットの探索

Chronic hypoxia in the tubulointerstitium serves as a final common pathway to end stage kidney disease in a variety of kidney diseases. Oxygen demand of the kidney is large, and the oxygen uptake efficiency of the kidney is relatively low due to arterio-venous oxygen shunt. Thus, the kidney can be hypoxic easily. In diseased kidneys, induction of hypoxia of the kidney is multifactorial. These factors include reduction of peritubular capillary blood flow due to activation of the renin-angiotensin system, increased oxygen consumption by tubular cells due to uremia, and renal anemia. Cells are endowed with the defensive mechanism against hypoxia, and hypoxia-inducible factor（HIF）serves as a master gene switch of various adaptive mechanisms, and activation of HIF induces a number of defensive responses in a coordinated manner. Many studies showed protective effects of HIF activation in experimental models of kidney disorders, and we are now performing detailed analysis of responses induced by HIF activation utilizing ChIP-Seq.