Muc1 is protective during kidney ischemia-reperfusion injury.

American journal of physiology. Renal physiology (2015-05-01)
Núria M Pastor-Soler, Timothy A Sutton, Henry E Mang, Carol L Kinlough, Sandra J Gendler, Cathy S Madsen, Sheldon I Bastacky, Jacqueline Ho, Mohammad M Al-Bataineh, Kenneth R Hallows, Sucha Singh, Satdarshan P Monga, Hanako Kobayashi, Volker H Haase, Rebecca P Hughey
摘要

Ischemia-reperfusion injury (IRI) due to hypotension is a common cause of human acute kidney injury (AKI). Hypoxia-inducible transcription factors (HIFs) orchestrate a protective response in renal endothelial and epithelial cells in AKI models. As human mucin 1 (MUC1) is induced by hypoxia and enhances HIF-1 activity in cultured epithelial cells, we asked whether mouse mucin 1 (Muc1) regulates HIF-1 activity in kidney tissue during IRI. Whereas Muc1 was localized on the apical surface of the thick ascending limb, distal convoluted tubule, and collecting duct in the kidneys of sham-treated mice, Muc1 appeared in the cytoplasm and nucleus of all tubular epithelia during IRI. Muc1 was induced during IRI, and Muc1 transcripts and protein were also present in recovering proximal tubule cells. Kidney damage was worse and recovery was blocked during IRI in Muc1 knockout mice compared with congenic control mice. Muc1 knockout mice had reduced levels of HIF-1α, reduced or aberrant induction of HIF-1 target genes involved in the shift of glucose metabolism to glycolysis, and prolonged activation of AMP-activated protein kinase, indicating metabolic stress. Muc1 clearly plays a significant role in enhancing the HIF protective pathway during ischemic insult and recovery in kidney epithelia, providing a new target for developing therapies to treat AKI. Moreover, our data support a role specifically for HIF-1 in epithelial protection of the kidney during IRI as Muc1 is present only in tubule epithelial cells.

材料
货号
品牌
产品描述

Sigma-Aldrich
羟乙基哌嗪乙硫磺酸, ≥99.5% (titration)
Sigma-Aldrich
氯化钠, BioXtra, ≥99.5% (AT)
Sigma-Aldrich
羟乙基哌嗪乙硫磺酸, BioPerformance Certified, ≥99.5% (titration), suitable for cell culture
Sigma-Aldrich
氯化钠, for molecular biology, DNase, RNase, and protease, none detected, ≥99% (titration)
Sigma-Aldrich
氯化钠, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99%
Sigma-Aldrich
氯化钠 溶液, 0.9% in water, BioXtra, suitable for cell culture
Sigma-Aldrich
氯化钠 溶液, 5 M in H2O, BioReagent, for molecular biology, suitable for cell culture
Sigma-Aldrich
HEPES缓冲溶液, 1 M in H2O
Sigma-Aldrich
氯化钠 溶液, 5 M
SAFC
氯化钠 溶液, 5 M
Sigma-Aldrich
抗 β-肌动蛋白抗体,小鼠单克隆, clone AC-15, purified from hybridoma cell culture
SAFC
羟乙基哌嗪乙硫磺酸
Sigma-Aldrich
氯化钠, meets analytical specification of Ph. Eur., BP, USP, 99.0-100.5%
Sigma-Aldrich
羟乙基哌嗪乙硫磺酸, BioUltra, for molecular biology, ≥99.5% (T)
Sigma-Aldrich
氯化钠, BioUltra, for molecular biology, ≥99.5% (AT)
Sigma-Aldrich
氯化钠 溶液, 0.85%
Sigma-Aldrich
氯化钠 溶液, BioUltra, for molecular biology, ~5 M in H2O
Sigma-Aldrich
氯化钠, 99.999% trace metals basis
Sigma-Aldrich
羟乙基哌嗪乙硫磺酸, BioXtra, pH 5.0-6.5 (1 M in H2O), ≥99.5% (titration)
SAFC
羟乙基哌嗪乙硫磺酸
Sigma-Aldrich
氯化钠, BioPerformance Certified, ≥99% (titration), suitable for insect cell culture, suitable for plant cell culture
Sigma-Aldrich
羟乙基哌嗪乙硫磺酸, BioXtra, suitable for mouse embryo cell culture, ≥99.5% (titration)
Sigma-Aldrich
羟乙基哌嗪乙硫磺酸, anhydrous, free-flowing, Redi-Dri, ≥99.5%
Sigma-Aldrich
氯化钠, tablet
Sigma-Aldrich
氯化钠, AnhydroBeads, −10 mesh, 99.999% trace metals basis
Sigma-Aldrich
氯化钠, random crystals, optical grade, 99.9% trace metals basis
Sigma-Aldrich
氯化钠, AnhydroBeads, −10 mesh, 99.99% trace metals basis
Sigma-Aldrich
抗AMPKα 1抗体, Upstate®, from rabbit
Sigma-Aldrich
氯化钠-35Cl, 99 atom % 35Cl