Myo-inositol Oxygenase (MIOX) Overexpression Drives the Progression of Renal Tubulointerstitial Injury in Diabetes
Tóm tắt
Conceivably, upregulation of myo-inositol oxygenase (MIOX) is associated with altered cellular redox. Its promoter includes oxidant-response elements, and we also discovered binding sites for XBP1, a transcription factor of endoplasmic reticulum (ER) stress response. Previous studies indicate that MIOX’s upregulation in acute tubular injury is mediated by oxidant and ER stress. Here, we investigated whether hyperglycemia leads to accentuation of oxidant and ER stress while these boost each other’s activities, thereby augmenting tubulointerstitial injury/fibrosis. We generated MIOX-overexpressing transgenic (MIOX-TG) and MIOX knockout (MIOX-KO) mice. A diabetic state was induced by streptozotocin administration. Also, MIOX-KO were crossbred with Ins2Akita to generate Ins2Akita/KO mice. MIOX-TG mice had worsening renal functions with kidneys having increased oxidant/ER stress, as reflected by DCF/dihydroethidium staining, perturbed NAD-to-NADH and glutathione-to-glutathione disulfide ratios, increased NOX4 expression, apoptosis and its executionary molecules, accentuation of TGF-β signaling, Smads and XBP1 nuclear translocation, expression of GRP78 and XBP1 (ER stress markers), and accelerated tubulointerstitial fibrosis. These changes were not seen in MIOX-KO mice. Interestingly, such changes were remarkably reduced in Ins2Akita/KO mice and, likewise, in vitro experiments with XBP1 siRNA. These findings suggest that MIOX expression accentuates, while its deficiency shields kidneys from, tubulointerstitial injury by dampening oxidant and ER stress, which mutually enhance each other’s activity.
Từ khóa
Tài liệu tham khảo
Brownlee, 2001, Biochemistry and molecular cell biology of diabetic complications, Nature, 414, 813, 10.1038/414813a
Sheetz, 2002, Molecular understanding of hyperglycemia’s adverse effects for diabetic complications, JAMA, 288, 2579, 10.1001/jama.288.20.2579
Reusch, 2003, Diabetes, microvascular complications, and cardiovascular complications: what is it about glucose, J Clin Invest, 112, 986, 10.1172/JCI200319902
LeRoith, 2004, Diabetes Mellitus: A Fundamental and Clinical Text, 3rd ed., 1
Sharma, 2016, Obesity and diabetic kidney disease: role of oxidant stress and redox balance, Antioxid Redox Signal, 25, 208, 10.1089/ars.2016.6696
Raj, 2000, Advanced glycation end products: a Nephrologist’s perspective, Am J Kidney Dis, 35, 365, 10.1016/S0272-6386(00)70189-2
Kato, 2016, An endoplasmic reticulum stress-regulated lncRNA hosting a microRNA megacluster induces early features of diabetic nephropathy, Nat Commun, 7, 12864, 10.1038/ncomms12864
Badal, 2014, New insights into molecular mechanisms of diabetic kidney disease, Am J Kidney Dis, 63, S63, 10.1053/j.ajkd.2013.10.047
Brosius, 2008, Is the ER stressed out in diabetic kidney disease, J Am Soc Nephrol, 19, 2040, 10.1681/ASN.2008090959
Peti-Peterdi, 2008, Activation of the renal renin-angiotensin system in diabetes--new concepts, Nephrol Dial Transplant, 23, 3047, 10.1093/ndt/gfn377
Fioretto, 2007, Histopathology of diabetic nephropathy, Semin Nephrol, 27, 195, 10.1016/j.semnephrol.2007.01.012
Mallipattu, 2016, The podocyte as a direct target for treatment of glomerular disease, Am J Physiol Renal Physiol, 311, F46, 10.1152/ajprenal.00184.2016
Fu, 2015, Glomerular endothelial cell injury and cross talk in diabetic kidney disease, Am J Physiol Renal Physiol, 308, F287, 10.1152/ajprenal.00533.2014
Zhan, 2015, Disruption of renal tubular mitochondrial quality control by Myo-inositol oxygenase in diabetic kidney disease, J Am Soc Nephrol, 26, 1304, 10.1681/ASN.2014050457
Kanwar, 2011, A glimpse of various pathogenetic mechanisms of diabetic nephropathy, Annu Rev Pathol, 6, 395, 10.1146/annurev.pathol.4.110807.092150
Wenzel, 1995, Activation of mesangial cells by the phosphatase inhibitor vanadate. Potential implications for diabetic nephropathy, J Clin Invest, 95, 1244, 10.1172/JCI117774
Forbes, 2013, Report on ISN forefronts, Melbourne, Australia, 4-7 October 2012: tubulointerstitial disease in diabetic nephropathy, Kidney Int, 84, 653, 10.1038/ki.2013.89
Gilbert, 2017, Proximal tubulopathy: prime mover and key therapeutic target in diabetic kidney disease, Diabetes, 66, 791, 10.2337/db16-0796
Sharma, 2018, Contribution of myo-inositol oxygenase in AGE:RAGE-mediated renal tubulointerstitial injury in the context of diabetic nephropathy, Am J Physiol Renal Physiol, 314, F107, 10.1152/ajprenal.00434.2017
Giacco, 2010, Oxidative stress and diabetic complications, Circ Res, 107, 1058, 10.1161/CIRCRESAHA.110.223545
Kashihara, 2010, Oxidative stress in diabetic nephropathy, Curr Med Chem, 17, 4256, 10.2174/092986710793348581
Ying, 2008, NAD+/NADH and NADP+/NADPH in cellular functions and cell death: regulation and biological consequences, Antioxid Redox Signal, 10, 179, 10.1089/ars.2007.1672
Cowley, 1990, In vivo osmoregulation of aldose reductase mRNA, protein, and sorbitol in renal medulla, Am J Physiol, 258, F154
Prabhu, 2005, Up-regulation of human myo-inositol oxygenase by hyperosmotic stress in renal proximal tubular epithelial cells, J Biol Chem, 280, 19895, 10.1074/jbc.M502621200
Nayak, 2005, Modulation of renal-specific oxidoreductase/myo-inositol oxygenase by high-glucose ambience, Proc Natl Acad Sci U S A, 102, 17952, 10.1073/pnas.0509089102
Nayak, 2011, Transcriptional and post-translational modulation of myo-inositol oxygenase by high glucose and related pathobiological stresses, J Biol Chem, 286, 27594, 10.1074/jbc.M110.217141
Chang, 2015, Renal depletion of myo-inositol is associated with its increased degradation in animal models of metabolic disease, Am J Physiol Renal Physiol, 309, F755, 10.1152/ajprenal.00164.2015
Tominaga, 2016, Transcriptional and translational modulation of myo-inositol oxygenase (Miox) by fatty acids: implications in renal tubular injury induced in obesity and diabetes, J Biol Chem, 291, 1348, 10.1074/jbc.M115.698191
Dutta, 2017, Beneficial effects of myo-inositol oxygenase deficiency in cisplatin-induced AKI, J Am Soc Nephrol, 28, 1421, 10.1681/ASN.2016070744
Yang, 2010, Polymorphisms of myo-inositol oxygenase gene are associated with Type 1 diabetes mellitus, J Diabetes Complications, 24, 404, 10.1016/j.jdiacomp.2009.09.005
Cunard, 2011, The endoplasmic reticulum stress response and diabetic kidney disease, Am J Physiol Renal Physiol, 300, F1054, 10.1152/ajprenal.00021.2011
Fan, 2017, The role of endoplasmic reticulum stress in diabetic nephropathy, Curr Diab Rep, 10.1007/s11892-017-0842-y
Hummasti, 2010, Endoplasmic reticulum stress and inflammation in obesity and diabetes, Circ Res, 107, 579, 10.1161/CIRCRESAHA.110.225698
Shu, 2018, Endoplasmic reticulum stress is activated in post-ischemic kidneys to promote chronic kidney disease, EBioMedicine, 37, 269, 10.1016/j.ebiom.2018.10.006
Tominaga, 2019, myo-Inositol oxygenase accentuates renal tubular injury initiated by endoplasmic reticulum stress, Am J Physiol Renal Physiol, 316, F301, 10.1152/ajprenal.00534.2018
Yamaguchi, 2007, An enzymatic cycling assay for nicotinic acid adenine dinucleotide phosphate using NAD synthetase, Anal Biochem, 364, 97, 10.1016/j.ab.2007.02.011
Forbes, 2008, Oxidative stress as a major culprit in kidney disease in diabetes, Diabetes, 57, 1446, 10.2337/db08-0057
Yang, 2008, Regulation of 3-phosphoinositide-dependent protein kinase-1 (PDK1) by Src involves tyrosine phosphorylation of PDK1 and Src homology 2 domain binding, J Biol Chem, 283, 1480, 10.1074/jbc.M706361200
Prasad, 2000, Oxidative stress and vanadate induce tyrosine phosphorylation of phosphoinositide-dependent kinase 1 (PDK1), Biochemistry, 39, 6929, 10.1021/bi000387i
Newton, 2003, Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm, Biochem J, 370, 361, 10.1042/bj20021626
Iglesias-De La Cruz, 2001, Hydrogen peroxide increases extracellular matrix mRNA through TGF-beta in human mesangial cells, Kidney Int, 59, 87, 10.1046/j.1523-1755.2001.00469.x
Ha, 2001, Activation of protein kinase c-delta and c-epsilon by oxidative stress in early diabetic rat kidney, Am J Kidney Dis, 38, S204, 10.1053/ajkd.2001.27446
Bhandary, 2012, An involvement of oxidative stress in endoplasmic reticulum stress and its associated diseases, Int J Mol Sci, 14, 434, 10.3390/ijms14010434
Yamaguchi, 2019, Nutritional supplementation with myo-inositol in growing mice specifically augments mandibular endochondral growth, Bone, 121, 181, 10.1016/j.bone.2019.01.020
Deng, 2019, myo-Inositol oxygenase expression profile modulates pathogenic ferroptosis in the renal proximal tubule, J Clin Invest, 129, 5033, 10.1172/JCI129903
Ratliff, 2016, Oxidant mechanisms in renal injury and disease, Antioxid Redox Signal, 25, 119, 10.1089/ars.2016.6665
Lash, 2015, Mitochondrial glutathione in diabetic nephropathy, J Clin Med, 4, 1428, 10.3390/jcm4071428
Bucana, 1986, Uptake and accumulation of the vital dye hydroethidine in neoplastic cells, J Histochem Cytochem, 34, 1109, 10.1177/34.9.2426339
Carter, 1994, Intracellular hydrogen peroxide and superoxide anion detection in endothelial cells, J Leukoc Biol, 55, 253, 10.1002/jlb.55.2.253
Sena, 2012, Physiological roles of mitochondrial reactive oxygen species, Mol Cell, 48, 158, 10.1016/j.molcel.2012.09.025
Wu, 2016, Sources and implications of NADH/NAD(+) redox imbalance in diabetes and its complications, Diabetes Metab Syndr Obes, 9, 145
Yan, 2018, Redox imbalance stress in diabetes mellitus: role of the polyol pathway, Animal Model Exp Med, 1, 7, 10.1002/ame2.12001
Kakkar, 1997, Antioxidant defense system in diabetic kidney: a time course study, Life Sci, 60, 667, 10.1016/S0024-3205(96)00702-3
Winiarska, 2004, Diabetes-induced changes in glucose synthesis, intracellular glutathione status and hydroxyl free radical generation in rabbit kidney-cortex tubules, Mol Cell Biochem, 261, 91, 10.1023/B:MCBI.0000028742.83086.43
Brownlee, 2005, The pathobiology of diabetic complications: a unifying mechanism, Diabetes, 54, 1615, 10.2337/diabetes.54.6.1615
Ott, 2007, Role of cardiolipin in cytochrome c release from mitochondria, Cell Death Differ, 14, 1243, 10.1038/sj.cdd.4402135
Han, 2017, Triptolide suppresses glomerular mesangial cell proliferation in diabetic nephropathy is associated with inhibition of PDK1/Akt/mTOR pathway, Int J Biol Sci, 13, 1266, 10.7150/ijbs.20485