Characterisation of the hydrogen sulfide system in early diabetic kidney disease

in Journal of Molecular Endocrinology
Authors:
Caroline J Bushell Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia

Search for other papers by Caroline J Bushell in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0002-1526-4848
,
Leonard G Forgan School of Medicine, Deakin University, Waurn Ponds, Australia

Search for other papers by Leonard G Forgan in
Current site
Google Scholar
PubMed
Close
,
Kathryn Aston-Mourney Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia

Search for other papers by Kathryn Aston-Mourney in
Current site
Google Scholar
PubMed
Close
,
Timothy Connor Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia

Search for other papers by Timothy Connor in
Current site
Google Scholar
PubMed
Close
,
Sean L McGee Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia

Search for other papers by Sean L McGee in
Current site
Google Scholar
PubMed
Close
, and
Bryony A McNeill Institute for Mental and Physical Health and Clinical Translation, Deakin University, Geelong, Australia

Search for other papers by Bryony A McNeill in
Current site
Google Scholar
PubMed
Close

Correspondence should be addressed to C J Bushell: c.bushell@research.deakin.edu.au
Restricted access
Rent on DeepDyve

Sign up for journal news

A deficiency in hydrogen sulfide has been implicated in the development and progression of diabetic chronic kidney disease. The purpose of this study was to determine the effect of diabetes on the H2S system in early-stage diabetic kidney disease. We characterised gene and protein expression profile of the enzymes that regulate H2S production and degradation, and H2S production capacity, in the kidney from 10-week-old C57BL6Jdb/db mice (n = 6), in age-matched heterozygous controls (n = 7), and in primary endothelial cells (HUVECs) exposed to high glucose. In db/db mice, renal H2S levels were significantly reduced (P = 0.009). Protein expression of the H2S production enzymes was differentially affected by diabetes: cystathionine β-synthase (CBS) was significantly lower in both db/db mice and high glucose-treated HUVECs (P < 0.0001; P = 0.0318) whereas 3-mercatopyruvate sulfurtransferase (3-MST) expression was higher in the db/db kidney (P < 0.0001), yet lower in the HUVECs (P = 0.0001). Diabetes had no effect on the expression of cystathionine γ-lyase (CSE) in the db/db kidney (P = ns) but was associated with reduced expression in the HUVECs (P = 0.0004). Protein expression of degradation enzyme sulfide quinone reductase (SQOR) was significantly higher in db/db kidney (P = 0.048) and lower in the high glucose-treated HUVECs (P = 0.008). Immunofluorescence studies revealed differential localisation of the H2S enzymes in the kidney, including both tubular and vascular localisation, suggestive of functionally distinct actions in the kidney. The results of this study provide foundational knowledge for future research looking at the H2S system in both kidney physiology and the aetiology of chronic diabetic kidney disease.

 

  • Collapse
  • Expand
  • Afsar B, Hornum M, Afsar RE, Ertuglu LA, Ortiz A, Covic A, van Raalte DH, Cherney DZI & & Kanbay M 2021 Mitochondrion-driven nephroprotective mechanisms of novel glucose lowering medications. Mitochondrion 58 7282. (https://doi.org/10.1016/j.mito.2021.02.016)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Agrawal N & & Banerjee R 2008 Human polycomb 2 protein is a SUMO E3 ligase and alleviates substrate-induced inhibition of cystathionine beta-synthase SUMOylation. PLoS One 3 e4032. (https://doi.org/10.1371/journal.pone.0004032)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ahmad FU, Sattar MA, Rathore HA, Abdullah MH, Tan S, Abdullah NA & & Johns EJ 2012 Exogenous hydrogen sulfide (H2S) reduces blood pressure and prevents the progression of diabetic nephropathy in spontaneously hypertensive rats. Renal Failure 34 203210. (https://doi.org/10.3109/0886022X.2011.643365)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ahmed HH, Taha FM, Omar HS, Elwi HM & & Abdelnasser M 2019 Hydrogen sulfide modulates SIRT1 and suppresses oxidative stress in diabetic nephropathy. Molecular and Cellular Biochemistry 457 19. (https://doi.org/10.1007/s11010-019-03506-x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bao L, Vlcek C, Paces V & & Kraus JP 1998 Identification and tissue distribution of human cystathionine beta-synthase mRNA isoforms. Archives of Biochemistry and Biophysics 350 95103. (https://doi.org/10.1006/abbi.1997.0486)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bauchet AL, Masson R, Guffroy M & & Slaoui M 2011 Immunohistochemical identification of kidney nephron segments in the dog, rat, mouse, and cynomolgus monkey. Toxicologic Pathology 39 11151128. (https://doi.org/10.1177/0192623311425060)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bełtowski J 2010 Hypoxia in the renal medulla: implications for hydrogen sulfide signaling. Journal of Pharmacology and Experimental Therapeutics 334 358363. (https://doi.org/10.1124/jpet.110.166637)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bogdanov P, Corraliza L, Villena JA, Carvalho AR, Garcia-Arumí J, Ramos D, Ruberte J, Simó R & & Hernández C 2014 The db/db mouse: a useful model for the study of diabetic retinal neurodegeneration. PLoS One 9 e97302. (https://doi.org/10.1371/journal.pone.0097302)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Chen Y, Lee K, Ni Z & & He JC 2020 Diabetic kidney disease: challenges, advances, and opportunities. Kidney Diseases 6 215225. (https://doi.org/10.1159/000506634)

  • Daehn IS 2018 Glomerular endothelial cell stress and cross-talk with podocytes in early diabetic kidney disease. Frontiers in Medicine 5 76. (https://doi.org/10.3389/fmed.2018.00076)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Di Camillo B, Puricelli L, Iori E, Toffolo GM, Tessari P & & Arrigoni G 2023 Modeling SILAC data to assess protein turnover in a cellular model of diabetic nephropathy. International Journal of Molecular Sciences 24 2811. (https://doi.org/10.3390/ijms24032811)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dominy JE & & Stipanuk MH 2004 New roles for cysteine and transsulfuration enzymes: production of H2S, a neuromodulator and smooth muscle relaxant. Nutrition Reviews 62 348353. (https://doi.org/10.1111/j.1753-4887.2004.tb00060.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ellwood RA, Hewitt JE, Torregrossa R, Philp AM, Hardee JP, Hughes S, van de Klashorst D, Gharahdaghi N, Anupom T, Slade L, et al.2021 Mitochondrial hydrogen sulfide supplementation improves health in the C. elegans Duchenne muscular dystrophy model. Proceedings of the National Academy of Sciences of the United States of America 118 e2018342118. (https://doi.org/10.1073/pnas.2018342118)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Feliers D, Lee HJ & & Kasinath BS 2016 Hydrogen sulfide in renal physiology and disease. Antioxidants and Redox Signaling 25 720731. (https://doi.org/10.1089/ars.2015.6596)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Forbes JM & & Thorburn DR 2018 Mitochondrial dysfunction in diabetic kidney disease. Nature Reviews. Nephrology 14 291312. (https://doi.org/10.1038/nrneph.2018.9)

  • Fräsdorf B, Radon C & & Leimkühler S 2014 Characterization and interaction studies of two isoforms of the dual localized 3-mercaptopyruvate sulfurtransferase TUM1 from humans. Journal of Biological Chemistry 289 3454334556. (https://doi.org/10.1074/jbc.M114.605733)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Han P, Zhan H, Shao M, Wang W, Song G, Yu X, Zhang C, Ge N, Yi T, Li S, et al.2018 Niclosamide ethanolamine improves kidney injury in db/db mice. Diabetes Research and Clinical Practice 144 2533. (https://doi.org/10.1016/j.diabres.2018.08.003)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hewitt SM, Baskin DG, Frevert CW, Stahl WL & & Rosa-Molinar E 2014 Controls for immunohistochemistry: the Histochemical Society’s standards of practice for validation of immunohistochemical assays. Journal of Histochemistry and Cytochemistry 62 693697. (https://doi.org/10.1369/0022155414545224)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Huang P, Chen S, Wang Y, Liu J, Yao Q, Huang Y, Li H, Zhu M, Wang S, Li L, et al.2015 Down-regulated CBS/H2S pathway is involved in high-salt-induced hypertension in Dahl rats. Nitric Oxide: Biology and Chemistry 46 192203. (https://doi.org/10.1016/j.niox.2015.01.004)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jackson MR, Melideo SL & & Jorns MS 2012 Human sulfide: quinone oxidoreductase catalyzes the first step in hydrogen sulfide metabolism and produces a sulfane sulfur metabolite. Biochemistry 51 68046815. (https://doi.org/10.1021/bi300778t)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Jain SK, Bull R, Rains JL, Bass PF, Levine SN, Reddy S, McVie R & & Bocchini JA Jr 2010 Low levels of hydrogen sulfide in the blood of diabetes patients and streptozotocin-treated rats causes vascular inflammation? Antioxidants and Redox Signaling 12 13331337. (https://doi.org/10.1089/ars.2009.2956)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kabil O, Zhou Y & & Banerjee R 2006 Human cystathionine β-synthase is a target for SUMOylation. Biochemistry 45 1352813536. (https://doi.org/10.1021/bi0615644)

  • Kakimoto T, Okada K, Hirohashi Y, Relator R, Kawai M, Iguchi T, Fujitaka K, Nishio M, Kato T, Fukunari A, et al.2014 Automated image analysis of a glomerular injury marker desmin in spontaneously diabetic Torii rats treated with losartan. Journal of Endocrinology 222 4351. (https://doi.org/10.1530/JOE-14-0164)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kasinath BS, Feliers D & & Lee HJ 2017 Hydrogen sulfide as a regulatory factor in kidney health and disease. Biochemical Pharmacology 149 2941. (https://doi.org/10.1016/j.bcp.2017.12.005)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kimura H 2014 The physiological role of hydrogen sulfide and beyond. Nitric Oxide: Biology and Chemistry 41 410. (https://doi.org/10.1016/j.niox.2014.01.002)

  • Koning AM, Frenay AR, Leuvenink HGD & & van Goor H 2015 Hydrogen sulfide in renal physiology, disease and transplantation – the smell of renal protection. Nitric Oxide: Biology and Chemistry 46 3749. (https://doi.org/10.1016/j.niox.2015.01.005)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kundu S, Pushpakumar SB, Tyagi A, Coley D & & Sen U 2013 Hydrogen sulfide deficiency and diabetic renal remodeling: role of matrix metalloproteinase-9. American Journal of Physiology-Endocrinology and Metabolism 304 E1365E1378. (https://doi.org/10.1152/ajpendo.00604.2012)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lassén E & & Daehn IS 2020 Molecular mechanisms in early diabetic kidney disease: glomerular endothelial cell dysfunction. International Journal of Molecular Sciences 21 9456. (https://doi.org/10.3390/ijms21249456)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Laxman S, Sutter BM, Wu X, Kumar S, Guo X, Trudgian DC, Mirzaei H & & Tu BP 2013 Sulfur amino acids regulate translational capacity and metabolic homeostasis through modulation of tRNA thiolation. Cell 154 416429. (https://doi.org/10.1016/j.cell.2013.06.043)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lee HJ, Mariappan MM, Feliers D, Cavaglieri RC, Sataranatarajan K, Abboud HE, Choudhury GG & & Kasinath BS 2012 Hydrogen sulfide inhibits high glucose-induced matrix protein synthesis by activating AMP-activated protein kinase in renal epithelial cells. Journal of Biological Chemistry 287 44514461. (https://doi.org/10.1074/jbc.M111.278325)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Leigh J, Juriasingani S, Akbari M, Shao P, Saha MN, Lobb I, Bachtler M, Fernandez B, Qian Z, van Goor H, et al.2019 Endogenous H(2)S production deficiencies lead to impaired renal erythropoietin production. Canadian Urological Association Journal 13 210219. (https://doi.org/10.5489/cuaj.5658)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Li H, Feng SJ, Zhang GZ & & Wang SX 2014 Correlation of lower concentrations of hydrogen sulfide with atherosclerosis in chronic hemodialysis patients with diabetic nephropathy. Blood Purification 38 188194. (https://doi.org/10.1159/000368883)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Li M, Nie L, Hu Y, Yan X, Xue L, Chen L, Zhou H & & Zheng Y 2013 Chronic intermittent hypoxia promotes expression of 3-mercaptopyruvate sulfurtransferase in adult rat medulla oblongata. Autonomic Neuroscience: Basic and Clinical 179 8489. (https://doi.org/10.1016/j.autneu.2013.08.066)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ligasová A & & Koberna K 2019 Quantification of fixed adherent cells using a strong enhancer of the fluorescence of DNA dyes. Scientific Reports 9 8701. (https://doi.org/10.1038/s41598-019-45217-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lu M, Liu YH, Goh HS, Wang JJX, Yong QC, Wang R & & Bian JS 2010 Hydrogen sulfide inhibits plasma renin activity. Journal of the American Society of Nephrology 21 9931002. (https://doi.org/10.1681/ASN.2009090949)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Markovic J, Borras C, Ortega A, Sastre J, Vina J & & Pallardo FV 2007 Glutathione is recruited into the nucleus in early phases of cell proliferation. Journal of Biological Chemistry 282 2041620424. (https://doi.org/10.1074/jbc.M609582200)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Módis K, Coletta C, Erdélyi K, Papapetropoulos A & & Szabo C 2013 Intramitochondrial hydrogen sulfide production by 3-mercaptopyruvate sulfurtransferase maintains mitochondrial electron flow and supports cellular bioenergetics. FASEB Journal 27 601611. (https://doi.org/10.1096/fj.12-216507)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ogunkola MO, Guiraudie-Capraz G, Feron F & & Leimkühler S 2023 The human mercaptopyruvate sulfurtransferase TUM1 is involved in Moco biosynthesis, cytosolic tRNA thiolation and cellular bioenergetics in human embryonic kidney cells. Biomolecules 13 144. (https://doi.org/10.3390/biom13010144)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Olson KR 2012 A practical look at the chemistry and biology of hydrogen sulfide. Antioxidants and Redox Signaling 17 3244. (https://doi.org/10.1089/ars.2011.4401)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Olson KR 2021 A case for hydrogen sulfide metabolism as an oxygen sensing mechanism. Antioxidants 10 1650. (https://doi.org/10.3390/antiox10111650)

  • Paul BD, Snyder SH & & Kashfi K 2021 Effects of hydrogen sulfide on mitochondrial function and cellular bioenergetics. Redox Biology 38 101772. (https://doi.org/10.1016/j.redox.2020.101772)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pedre B & & Dick TP 2021 3-mercaptopyruvate sulfurtransferase: an enzyme at the crossroads of sulfane sulfur trafficking. Biological Chemistry 402 223237. (https://doi.org/10.1515/hsz-2020-0249)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sharma K, McCue P & & Dunn SR 2003 Diabetic kidney disease in the db/dbmouse. American Journal of Physiology-Renal Physiology 284 F1138F1144. (https://doi.org/10.1152/ajprenal.00315.2002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shen W, Gao C, Cueto R, Liu L, Fu H, Shao Y, Yang WY, Fang P, Choi ET, Wu Q, et al.2020 Homocysteine-methionine cycle is a metabolic sensor system controlling methylation-regulated pathological signaling. Redox Biology 28 101322. (https://doi.org/10.1016/j.redox.2019.101322)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, Stein C, Basit A, Chan JCN, Mbanya JC, et al.2022 IDF Diabetes Atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Research and Clinical Practice 183 109119. (https://doi.org/10.1016/j.diabres.2021.109119)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sutariya B, Jhonsa D & & Saraf MN 2016 TGF-β: the connecting link between nephropathy and fibrosis. Immunopharmacology and Immunotoxicology 38 3949. (https://doi.org/10.3109/08923973.2015.1127382)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Suzuki K, Sagara M, Aoki C, Tanaka S & & Aso Y 2017 Clinical implication of plasma hydrogen sulfide levels in Japanese patients with type 2 diabetes. Internal Medicine (Tokyo, Japan) 56 1721. (https://doi.org/10.2169/internalmedicine.56.7403)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Szabo C, Coletta C, Chao C, Módis K, Szczesny B, Papapetropoulos A & & Hellmich MR 2013 Tumor-derived hydrogen sulfide, produced by cystathionine-β-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer. Proceedings of the National Academy of Sciences of the United States of America 110 1247412479. (https://doi.org/10.1073/pnas.1306241110)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tao B, Wang R, Sun C & & Zhu Y 2017 3-mercaptopyruvate sulfurtransferase, not cystathionine β-synthase nor cystathionine γ-lyase, mediates hypoxia-induced migration of vascular endothelial cells. Frontiers in Pharmacology 8 657. (https://doi.org/10.3389/fphar.2017.00657)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Teng H, Wu B, Zhao K, Yang G, Wu L & & Wang R 2013 Oxygen-sensitive mitochondrial accumulation of cystathionine β-synthase mediated by Lon protease. Proceedings of the National Academy of Sciences 110 1267912684. (https://doi.org/10.1073/pnas.1308487110)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Thomas MC, Brownlee M, Susztak K, Sharma K, Jandeleit-Dahm KA, Zoungas S, Rossing P, Groop PH & & Cooper ME 2015 Diabetic kidney disease. Nature Reviews. Disease Primers 1 15018. (https://doi.org/10.1038/nrdp.2015.18)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Trautwein B, Merz T, Denoix N, Szabo C, Calzia E, Radermacher P & & McCook O 2021 3MST and the regulation of cardiac CSE and OTR expression in trauma and hemorrhage. Antioxidants 10 233. (https://doi.org/10.3390/antiox10020233)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Uyy E, Suica VI, Boteanu RM, Safciuc F, Cerveanu-Hogas A, Ivan L, Stavaru C, Simionescu M & & Antohe F 2020 Diabetic nephropathy associates with deregulation of enzymes involved in kidney sulphur metabolism. Journal of Cellular and Molecular Medicine 24 1213112140. (https://doi.org/10.1111/jcmm.15855)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • van den Born JC, Frenay AR, Bakker SJL, Pasch A, Hillebrands JL, Lambers Heerspink HJ & & van Goor H 2016 High. Nitric Oxide: Biology and Chemistry 55–56 1824. (https://doi.org/10.1016/j.niox.2016.03.001)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Venardos K, De Jong KA, Elkamie M, Connor T & & McGee SL 2015 The PKD inhibitor CID755673 enhances cardiac function in diabetic db/db mice. PLoS One 10 e0120934. (https://doi.org/10.1371/journal.pone.0120934)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Vinovskis C, Li LP, Prasad P, Tommerdahl K, Pyle L, Nelson RG, Pavkov ME, van Raalte D, Rewers M, Pragnell M, et al.2020 Relative hypoxia and early diabetic kidney disease in type 1 diabetes. Diabetes 69 27002708. (https://doi.org/10.2337/db20-0457)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wang Y, Yu R, Wu L & & Yang G 2020 Hydrogen sulfide signaling in regulation of cell behaviors. Nitric Oxide: Biology and Chemistry 103 919. (https://doi.org/10.1016/j.niox.2020.07.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wilson MO, McNeill BA, Barrell GK, Prickett TCR & & Espiner EA 2017 Dexamethasone increases production of C-type natriuretic peptide in the sheep brain. Journal of Endocrinology 235 1525. (https://doi.org/10.1530/JOE-17-0148)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yadav PK, Yamada K, Chiku T, Koutmos M & & Banerjee R 2013 Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. Journal of Biological Chemistry 288 2000220013. (https://doi.org/10.1074/jbc.M113.466177)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yamamoto J, Sato W, Kosugi T, Yamamoto T, Kimura T, Taniguchi S, Kojima H, Maruyama S, Imai E & & Matsuo S 2013 Distribution of hydrogen sulfide (H2S)-producing enzymes and the roles of the H2S donor sodium hydrosulfide in diabetic nephropathy. Clinical and Experimental Nephrology 17 3240. (https://doi.org/10.1007/s10157-012-0670-y)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yuan P, Xue H, Zhou L, Qu L, Li C, Wang Z, Ni J, Yu C, Yao T, Huang Y, et al.2011 Rescue of mesangial cells from high glucose-induced over-proliferation and extracellular matrix secretion by hydrogen sulfide. Nephrology, Dialysis, Transplantation 26 21192126. (https://doi.org/10.1093/ndt/gfq749)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Yuan X, Zhang J, Xie F, Tan W, Wang S, Huang L, Tao L, Xing Q & & Yuan Q 2017 Loss of the protein cystathionine β-synthase during kidney injury promotes renal tubulointerstitial fibrosis. Kidney and Blood Pressure Research 42 428443. (https://doi.org/10.1159/000479295)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zhang P, Yao Q, Lu L, Li Y, Chen PJ & & Duan C 2014 Hypoxia-inducible factor 3 is an oxygen-dependent transcription activator and regulates a distinct transcriptional response to hypoxia. Cell Reports 6 11101121. (https://doi.org/10.1016/j.celrep.2014.02.011)

    • PubMed
    • Search Google Scholar
    • Export Citation