Administration of dexamethasone protects mice against ischemia/reperfusion induced renal injury by suppressing PI3K/AKT signaling.
Dexamethasone (DEX), a ligand for glucocorticoid receptor (GR), has long been used in the clinical practice due to its anti-inflammatory and immunosuppressive properties. Given that ischemia/reperfusion (IR)-induced renal injury is featured by the excessive immune response; the current study is therefore designed to address the impact of dexamethasone on IR-induced renal injury, a common disorder in the clinical settings. Precondition of mice with 4 mg/kg of dexamethasone significantly attenuated IR-induced injury as manifested by the improved renal function along with ameliorated pathological changes and suppressed inflammatory infiltration. Mechanistic studies revealed that dexamethasone promotes GR activation, and by which it attenuates the signals for PI3K/AKT activation. Attenuated PI3K/AKT signaling thus suppresses inflammatory response which then protects kidneys from IR-induced injury. All together, our data support that dexamethasone could be a good alternative therapy for prevention and treatment of IR-induced renal injury in the clinical practice.
Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, People's Republic of China.
Jiong
J
Zhang
Ying
Y
Yao
Fang
F
Xiao
Xiaoqin
X
Lan
Chong
C
Yu
Ying
Y
Zhang
Cao
C
Jiang
Juan
J
Yang
Guangchang
G
Pei
Yueqiang
Y
Li
Song
S
Rong
Shuang
S
Hu
Junhua
J
Li
Gang
G
Xu
D058186:Acute Kidney Injury / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000378:metabolism; D015427:Reperfusion Injury / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects*
D016207:Cytokines; D005938:Glucocorticoids; D018836:Inflammation Mediators; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
Inflammatory response; PI3K/AKT signaling; dexamethasone; glucocorticoid receptor; ischemia/reperfusion injury