THE RELATİONSHİP OF HYPERGLYCEMİA WİTH EPİGENETİC MECHANİSMS
Yıl 2023,
Cilt: 30 Sayı: 3, 582 - 591, 23.09.2023
Esma Selçuk
,
Didem Özkahraman
,
Yudi Gebri Foenna
,
Nilüfer Şahin Calapoğlu
Öz
Epigenetics are traits that are inherited and reflected
in the phenotype, independent of the DNA sequence.
There is a genetic predisposition to hyperglycemia;
however, the environment plays critical roles in its
development and progress. Epigenetic changes
often translate environmental stimuli into changes in
gene expression. Epigenetic factors are mainly DNA
methylation, histone modifications and microRNAs.
Epigenetic changes, which play a role in the regulation
of all biological processes, are closely related
to diseases such as autoimmune/inflammatory,
cardiovascular, cancer, obesity and type 2 diabetes,
which are among the most important health problems
in the world and in our country. In particular, chronic
hyperglycemia, which plays a role in the pathogen of
diabetes and diabetes-related complications, affects
gene transcription through epigenetic mechanisms
such as DNA methylation, histone modifications
and microRNAs. In this review, we focused on
explaining the effects of hyperglycemia on epigenetic
mechanisms and the role of epigenetic changes it
causes in the pathogenesis of diseases.
Kaynakça
- 1. Villegas-Valverde CC, Kokuina E, Breff-Fonseca MC. Strengthening National Health Priorities for Diabetes Prevention and Management. MEDICC Rev. 2018;20(4):5.
- 2. Cugalj Kern B, Trebušak Podkrajšek K, Kovaˇc J, Šket R, Jenko
Bizjan B, Tesovnik T, Debeljak M, Battelino T, Bratina N. The
Role of Epigenetic Modifications in Late Complications in Type
1 Diabetes. Genes. 2022;13:705.
- 3. D’Urso A, Brickner J. Epigenetic transcriptional memory. Curr
Genet. 2017; 63:435–439.
- 4. Prandi FR, Lecis D, Illuminato F, Milite M, Celotto R, Lerakis S,
Romeo F, Barillà F. Epigenetic Modifications and Non-Coding
RNA in Diabetes-Mellitus-Induced Coronary Artery Disease:
Pathophysiological Link and New Therapeutic Frontiers. Int. J.
Mol. Sci. 2022, 23, 4589.
- 5. Klimontov VV, Saik OV, Korbut AI. Glucose Variability: How
Does It Work? Int. J. Mol. Sci. 2021;22:7783.
- 6. Khan RMM, Chua ZJY, Tan JC, Yang Y, Liao Z, Zhao Y. From
Pre-Diabetes to Diabetes: Diagnosis, Treatments and Translational
Research. Medicina. 2019;55:546.
- 7. Hammer M, Storey S, Hershey DS, Brady VJ, Davis E, Mandolfo
N, Bryant AL, Olausson J. Hyperglycemia and Cancer: A State-
of-the-Science Review. Oncol Nurs Forum. 2019;46(4):459-
472.
- 8. Jia G, Whaley-Connell A, R. Sowers J. Diabetic cardiomyopathy:
a hyperglycaemia- and insulinresistance-induced heart diseas.
Diabetologia. 2018;61(1): 21–28.
- 9. Kang Q, Yang C. Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications. Redox Biology. 2020;37:101799.
- 10. Çetiner Ö, Rakıcıoğlu N. Hiperglisemi, Oksidatif Stres ve Tip
2 Diyabette Oksidatif Stres Belirteçlerinin Tanımlanması. Oksidatif
Stres ve Tip 2 Diyabette Oksidatif Stres Belirteçlerinin
Tanımlanması. Türk Diyab Obez. 2020;1:60-68.
- 11. Venugopal S. Hyperglycemic memory and its long-term effects
in diabetes. Biomed. Res. 2016;2016:S354–361.
- 12. Diabetes Control and Complications Trial Research Group. Effect of intensive diabetes treatment on the development and
progression of long-term complications in adolescents with
insulin-dependent diabetes mellitus: Diabetes Control and
Complications Trial. J. Pediatr. 1994;125:177–188.
- 13. Testa R, Bonfigli AR, Prattichizzo F, La Sala L, De Nigris V,
Ceriello A. The “Metabolic Memory” Theory and the Early Treatment
of Hyperglycemia in Prevention of Diabetic Complications.
Nutrients. 2017;9:437
- 14. Nathan DM. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: Overview. Diabetes Care. 2014;37:9–16.
- 15. Franzago M, Fraticelli F, Stuppia L, Vitacolonna E. Nutrigenetics,
epigenetics and gestational diabetes: consequences in mother
and child. Epigenetics. 2019;14(3):215-235.
- 16. Tzika E, Dreker T, Imhof A. Epigenetics and Metabolism in Health
and Disease. Front. Genet. 2018;9:361.
- 17. Singh R, Chandel S, Dey D, Ghosh A, Roy S, Ravichandiran
V, Ghosh D. Epigenetic modification and therapeutic targets of
diabetes mellitus. Bioscience Reports. 2020;40:BSR20202160.
- 18. Livingstone C, Borai A. Insulin-like growth factor-II: its role in metabolic and endocrine disease. Clin. Endocrinol. 2014;80:773–
781.
- 19. Sparago A, Cerrato F, Vernucci M, Ferrero GB, Silengo MC,
Riccio A. Microdeletions in the human H19 DMR result in loss
of IGF2 imprinting and Beckwith-Wiedemann syndrome. Nat.
Genet. 2004;36:958–960.
- 20. Mokbel N, Hoffman NJ, Girgis CM, Small L, Turner N, Daly RJ,
et al. Grb10 deletion enhances muscle cell proliferation, differentiation and GLUT4 plasma membrane translocation. J. Cell.
Physiol. 2014;229:1753–1764.
- 21. Zhang S, Rattanatray L, McMillen IC, Suter CM, Morrison JL.
Periconceptional nutrition and the early programming of a life
of obesity or adversity. Prog. Biophys. Mol. Biol. 2011;106:307–314.
- 22. Charalambous M, Hernandez A. Genomic imprinting of the type
3 thyroid hormone deiodinase gene: regulation and developmental implications. Biochim. Biophys. Acta 2013;1830:3946–3955.
- 23. T. Keating S, El-Osta A. Epigenetics and Metabolism. Circ Res.
2015;116:715-736.
- 24. Can Mİ, Aslan A. Epigenetik Mekanizmalar ve Bazı Güncel Çalışmalar. Karaelmas Fen Müh. Derg. 2016; 6(2):445-452.
- 25. İmre KE, Akyol Mutlu A. Epigenetik Mekanizmalar: Maternal
Makro Besin Ögesi Alımının Etkileri. Bes Diy Derg.
2022;50(1):92-100.
- 26. Bell CG, Teschendorff AE, Rakyan VK, Maxwell AP, Beck S,
Savage DA. Genome-wide DNA methylation analysis for diabetic
nephropathy in type 1 diabetes mellitus. BMC Med. Genom.
2010;3:33.
- 27. Brennan EP, Ehrich M, Brazil DP, Crean JK, Murphy M, Sadlier
DM, Martin F, Godson C, van den Boom D, Maxwell AP, et al.
DNA methylation profiling in cell models of diabetic nephropathy.
Epigenetics. 2010;5:396–401.
- 28. Dalfrà MG, Burlina S, Del Vescovo GG, Lapolla A. Genetics
and Epigenetics: New Insight on Gestational Diabetes Mellitus.
Front. Endocrinol. 2020;11:602477.
- 29. Doğan R, Aktaş RG. Epigenetik Mekanizmalar ve Hepatosellüler
Karsinoma. Maltepe Tıp Dergisi. 2016;8:3.
- 30. Tessarz P, Kouzarides T. Histone core modifications regulating
nucleosome structure and dynamics. Nat. Rev. Mol. Cell Biol.
2014;15:703–708.
- 31. Bannister AJ, Kouzarides T. Regulation of chromatin by histone
modifications. Cell Res. 2011;21:381–395.
- 32. Barnes CE, English DM, Cowley SM. Acetylation and Co: An
expanding repertoire of histone acylations regulates chromatin
and transcription. Essays Biochem. 2019;63:97–107.
- 33. Rossetto D, Avvakumov N, Côté J. Histone phosphorylation.
Epigenetics. 2012;7:1098–1108.
- 34. Greer EL, Shi Y. Histone methylation: A dynamic mark in health,
disease and inheritance. Nat. Rev. Genet. 2012;13:343–357.
- 35. Cao J, Yan Q. Histone ubiquitination and deubiquitination in
transcription, DNA damage response, and cancer. Front. Oncol.
2012;2:1–9.
- 36. Cobos SN, Bennett SA, Torrente MP. The impact of histone
post-translational modifications in neurodegenerative diseases.
Biochim. Biophys. Acta Mol. Basis Dis. 2019;1865:1982–1991.
- 37. Wang Y, Yuan Q, Xie L. Histone Modifications in Aging: The
Underlying Mechanisms and Implications. Curr. Stem Cell Res.
Ther. 2018;13:125–135.
- 38. Audia JE, Campbell RM. Histone modifications and cancer.
Cold Spring Harb. Perspect. Biol. 2016;8:1–31.
- 39. Miao F, Wu X, Zhang L, Yuan YC, Riggs AD, Natarajan R. Genome-
wide analysis of histone lysine methylation variations
caused by diabetic conditions in human monocytes. J. Biol.
Chem. 2007;282:13854–13863.
- 40. Miao F, Chen Z, Genuth S, et al. Evaluating the role of epigenetic
histone modifications in the metabolic memory of type 1
diabetes. Diabetes. 2014;63:1748–1762.
- 41. Sun G, Reddy MA, Yuan H, Lanting L, Kato M, Natarajan R.
Epigenetic histone methylation modulates fibrotic gene expression.J. Am. Soc. Nephrol. 2010;21:2069–2080.
- 42. Li X, Li C, Li X, et al. Involvement of histone lysine methylation
in p21 gene expression in rat kidney in vivo and rat mesangial
cells in vitro under diabetic conditions. J. Diabetes Res.
2016;2016:3853242.
- 43. Chen J, Guo Y, Zeng W, et al. ER stress triggers MCP-1 expression
through SET7 / 9-induced histone methylation in the
kidneys of db / db mice. Am. J. Physiol. 2014;306:916–925.
- 44. Li Y, Reddy MA, Miao F, et al. Role of the histone H3 lysine 4
methyltransferase, SET7/9, in the regulation of NF-κB-dependent
inflammatory genes: Relevance to diabetes and inflammation.
J. Biol. Chem. 2008;283:26771–26781
- 45. Villeneuve LM, Reddy MA, et al. Epigenetic histone H3 lysine 9
methylation in metabolic memory and inflammatory phenotype
of vascular smooth muscle cells in diabetes. Proc. Natl. Acad.
Sci. 2008;105:9047–9052.
- 46. Jia Y, Reddy MA, Das S, et al. Dysregulation of histone H3 lysine
27 trimethylation in transforming growth factor-β1-induced
gene expression in mesangial cells and diabetic kidney. J. Biol.
Chem. 2019;294:12695–12707.
- 47. Lin SH, Ho WT, Wang YT, et al. Histone methyltransferase
Suv39h1 attenuates high glucose-induced fibronectin
and p21WAF1 in mesangial cells. Int. J. Biochem. Cell Biol.
2016;78:96–105.
- 48. Syreeni A, El-Osta A, Forsblom C, et al. Genetic examination
of SETD7 and SUV39H1/H2 methyltransferases and the risk of
diabetes complications in patients with type 1 diabetes. Diabetes.
2011; 60:3073–3080.
- 49. Bijkerk R, Duijs JMGJ, Khairoun M, et al. Circulating MicroRNAs
associate with diabetic nephropathy and systemic microvascular
damage and normalize after simultaneous pancreas-kidney
transplantation. Am. J. Transplant. 2015;15:1081–1090.
- 50. Assmann TS, Recamonde-Mendoza M, Costa AR, et al. Circulating miRNAs in diabetic kidney disease: Case–control study
and in silico analyses. Acta Diabetol. 2019;56:55–65.
- 51. Zampetaki A, Willeit P, Burr S, et al. Angiogenic microRNAs
linked to incidence and progression of diabetic retinopathy in
type 1 diabetes. Diabetes. 2016;65:216–227.
- 52. Santos-Bezerra DP, Santos AS, Guimarães, GC, et al. Micro-RNAs
518d-3p and 618 are upregulated in individuals with type
1 diabetes with multiple microvascular complications. Front.
Endocrinol. 2019;10:385.
- 53. Bera A, Das F, Ghosh-Choudhury N, Mariappan MM, Kasinath
BS, Choudhury GG. Reciprocal regulation of miR-214 and
PTEN by high glucose regulates renal glomerular mesangial
and proximal tubular epithelial cell hypertrophy and matrix expansion. Am. J. Physiol. Cell Physiol. 2017;313:C430–447.
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RJ. MicroRNA-377 is up-regulated and can lead to increased
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HİPERGLİSEMİNİN EPİGENETİK MEKANİZMALAR İLE İLİŞKİSİ
Yıl 2023,
Cilt: 30 Sayı: 3, 582 - 591, 23.09.2023
Esma Selçuk
,
Didem Özkahraman
,
Yudi Gebri Foenna
,
Nilüfer Şahin Calapoğlu
Öz
Epigenetik, DNA dizisinden bağımsız olarak fenotipe
yansıyan ve kalıtsal olarak aktarılabilen özelliklerdir.
Hiperglisemide genetik yatkınlık söz konusudur; ancak
çevre, gelişmesinde ve ilerlemesinde kritik roller
oynar. Epigenetik değişiklikler genellikle çevresel uyaranları
gen ifadesindeki değişikliklere çevirir. Epigenetik
faktörler, temel olarak DNA metilasyonu, histon
modifikasyonları ve mikroRNA'lardır. Tüm biyolojik
süreçlerin düzenlenmesinde rol oynayan epigenetik
değişiklikler, otoimmüne/inflamatuar, kardiyovasküler,
kanser, obezite ve tip 2 diyabet gibi tüm dünyada ve
ülkemizde önemli sağlık sorunlarının başında gelen
hastalıklar ile de yakından ilişkilidir. Özellikle diyabet
ve diyabetle ilişkili komplikasyonların patojeninizde rol
oynayan kronik hiperglisemi, DNA metilasyonu, histon
modifikasyonları ve mikro RNA’lar gibi epigenetik
mekanizmalar aracılığıyla gen transkripsiyonunu etkilemektedir.
Bu derlemede, hipergliseminin, epigenetik
mekanizmalar üzerindeki etkilerine ve yol açtığı epigenetik
değişimlerin hastalıklarların patogenezindeki
rollerini açıklamaya odaklandık.
Teşekkür
Bu çalışmada emeği geçen, değerli hocamız Prof. Dr. Mustafa CALAPOĞLU'na teşekkür ederiz.
Kaynakça
- 1. Villegas-Valverde CC, Kokuina E, Breff-Fonseca MC. Strengthening National Health Priorities for Diabetes Prevention and Management. MEDICC Rev. 2018;20(4):5.
- 2. Cugalj Kern B, Trebušak Podkrajšek K, Kovaˇc J, Šket R, Jenko
Bizjan B, Tesovnik T, Debeljak M, Battelino T, Bratina N. The
Role of Epigenetic Modifications in Late Complications in Type
1 Diabetes. Genes. 2022;13:705.
- 3. D’Urso A, Brickner J. Epigenetic transcriptional memory. Curr
Genet. 2017; 63:435–439.
- 4. Prandi FR, Lecis D, Illuminato F, Milite M, Celotto R, Lerakis S,
Romeo F, Barillà F. Epigenetic Modifications and Non-Coding
RNA in Diabetes-Mellitus-Induced Coronary Artery Disease:
Pathophysiological Link and New Therapeutic Frontiers. Int. J.
Mol. Sci. 2022, 23, 4589.
- 5. Klimontov VV, Saik OV, Korbut AI. Glucose Variability: How
Does It Work? Int. J. Mol. Sci. 2021;22:7783.
- 6. Khan RMM, Chua ZJY, Tan JC, Yang Y, Liao Z, Zhao Y. From
Pre-Diabetes to Diabetes: Diagnosis, Treatments and Translational
Research. Medicina. 2019;55:546.
- 7. Hammer M, Storey S, Hershey DS, Brady VJ, Davis E, Mandolfo
N, Bryant AL, Olausson J. Hyperglycemia and Cancer: A State-
of-the-Science Review. Oncol Nurs Forum. 2019;46(4):459-
472.
- 8. Jia G, Whaley-Connell A, R. Sowers J. Diabetic cardiomyopathy:
a hyperglycaemia- and insulinresistance-induced heart diseas.
Diabetologia. 2018;61(1): 21–28.
- 9. Kang Q, Yang C. Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications. Redox Biology. 2020;37:101799.
- 10. Çetiner Ö, Rakıcıoğlu N. Hiperglisemi, Oksidatif Stres ve Tip
2 Diyabette Oksidatif Stres Belirteçlerinin Tanımlanması. Oksidatif
Stres ve Tip 2 Diyabette Oksidatif Stres Belirteçlerinin
Tanımlanması. Türk Diyab Obez. 2020;1:60-68.
- 11. Venugopal S. Hyperglycemic memory and its long-term effects
in diabetes. Biomed. Res. 2016;2016:S354–361.
- 12. Diabetes Control and Complications Trial Research Group. Effect of intensive diabetes treatment on the development and
progression of long-term complications in adolescents with
insulin-dependent diabetes mellitus: Diabetes Control and
Complications Trial. J. Pediatr. 1994;125:177–188.
- 13. Testa R, Bonfigli AR, Prattichizzo F, La Sala L, De Nigris V,
Ceriello A. The “Metabolic Memory” Theory and the Early Treatment
of Hyperglycemia in Prevention of Diabetic Complications.
Nutrients. 2017;9:437
- 14. Nathan DM. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: Overview. Diabetes Care. 2014;37:9–16.
- 15. Franzago M, Fraticelli F, Stuppia L, Vitacolonna E. Nutrigenetics,
epigenetics and gestational diabetes: consequences in mother
and child. Epigenetics. 2019;14(3):215-235.
- 16. Tzika E, Dreker T, Imhof A. Epigenetics and Metabolism in Health
and Disease. Front. Genet. 2018;9:361.
- 17. Singh R, Chandel S, Dey D, Ghosh A, Roy S, Ravichandiran
V, Ghosh D. Epigenetic modification and therapeutic targets of
diabetes mellitus. Bioscience Reports. 2020;40:BSR20202160.
- 18. Livingstone C, Borai A. Insulin-like growth factor-II: its role in metabolic and endocrine disease. Clin. Endocrinol. 2014;80:773–
781.
- 19. Sparago A, Cerrato F, Vernucci M, Ferrero GB, Silengo MC,
Riccio A. Microdeletions in the human H19 DMR result in loss
of IGF2 imprinting and Beckwith-Wiedemann syndrome. Nat.
Genet. 2004;36:958–960.
- 20. Mokbel N, Hoffman NJ, Girgis CM, Small L, Turner N, Daly RJ,
et al. Grb10 deletion enhances muscle cell proliferation, differentiation and GLUT4 plasma membrane translocation. J. Cell.
Physiol. 2014;229:1753–1764.
- 21. Zhang S, Rattanatray L, McMillen IC, Suter CM, Morrison JL.
Periconceptional nutrition and the early programming of a life
of obesity or adversity. Prog. Biophys. Mol. Biol. 2011;106:307–314.
- 22. Charalambous M, Hernandez A. Genomic imprinting of the type
3 thyroid hormone deiodinase gene: regulation and developmental implications. Biochim. Biophys. Acta 2013;1830:3946–3955.
- 23. T. Keating S, El-Osta A. Epigenetics and Metabolism. Circ Res.
2015;116:715-736.
- 24. Can Mİ, Aslan A. Epigenetik Mekanizmalar ve Bazı Güncel Çalışmalar. Karaelmas Fen Müh. Derg. 2016; 6(2):445-452.
- 25. İmre KE, Akyol Mutlu A. Epigenetik Mekanizmalar: Maternal
Makro Besin Ögesi Alımının Etkileri. Bes Diy Derg.
2022;50(1):92-100.
- 26. Bell CG, Teschendorff AE, Rakyan VK, Maxwell AP, Beck S,
Savage DA. Genome-wide DNA methylation analysis for diabetic
nephropathy in type 1 diabetes mellitus. BMC Med. Genom.
2010;3:33.
- 27. Brennan EP, Ehrich M, Brazil DP, Crean JK, Murphy M, Sadlier
DM, Martin F, Godson C, van den Boom D, Maxwell AP, et al.
DNA methylation profiling in cell models of diabetic nephropathy.
Epigenetics. 2010;5:396–401.
- 28. Dalfrà MG, Burlina S, Del Vescovo GG, Lapolla A. Genetics
and Epigenetics: New Insight on Gestational Diabetes Mellitus.
Front. Endocrinol. 2020;11:602477.
- 29. Doğan R, Aktaş RG. Epigenetik Mekanizmalar ve Hepatosellüler
Karsinoma. Maltepe Tıp Dergisi. 2016;8:3.
- 30. Tessarz P, Kouzarides T. Histone core modifications regulating
nucleosome structure and dynamics. Nat. Rev. Mol. Cell Biol.
2014;15:703–708.
- 31. Bannister AJ, Kouzarides T. Regulation of chromatin by histone
modifications. Cell Res. 2011;21:381–395.
- 32. Barnes CE, English DM, Cowley SM. Acetylation and Co: An
expanding repertoire of histone acylations regulates chromatin
and transcription. Essays Biochem. 2019;63:97–107.
- 33. Rossetto D, Avvakumov N, Côté J. Histone phosphorylation.
Epigenetics. 2012;7:1098–1108.
- 34. Greer EL, Shi Y. Histone methylation: A dynamic mark in health,
disease and inheritance. Nat. Rev. Genet. 2012;13:343–357.
- 35. Cao J, Yan Q. Histone ubiquitination and deubiquitination in
transcription, DNA damage response, and cancer. Front. Oncol.
2012;2:1–9.
- 36. Cobos SN, Bennett SA, Torrente MP. The impact of histone
post-translational modifications in neurodegenerative diseases.
Biochim. Biophys. Acta Mol. Basis Dis. 2019;1865:1982–1991.
- 37. Wang Y, Yuan Q, Xie L. Histone Modifications in Aging: The
Underlying Mechanisms and Implications. Curr. Stem Cell Res.
Ther. 2018;13:125–135.
- 38. Audia JE, Campbell RM. Histone modifications and cancer.
Cold Spring Harb. Perspect. Biol. 2016;8:1–31.
- 39. Miao F, Wu X, Zhang L, Yuan YC, Riggs AD, Natarajan R. Genome-
wide analysis of histone lysine methylation variations
caused by diabetic conditions in human monocytes. J. Biol.
Chem. 2007;282:13854–13863.
- 40. Miao F, Chen Z, Genuth S, et al. Evaluating the role of epigenetic
histone modifications in the metabolic memory of type 1
diabetes. Diabetes. 2014;63:1748–1762.
- 41. Sun G, Reddy MA, Yuan H, Lanting L, Kato M, Natarajan R.
Epigenetic histone methylation modulates fibrotic gene expression.J. Am. Soc. Nephrol. 2010;21:2069–2080.
- 42. Li X, Li C, Li X, et al. Involvement of histone lysine methylation
in p21 gene expression in rat kidney in vivo and rat mesangial
cells in vitro under diabetic conditions. J. Diabetes Res.
2016;2016:3853242.
- 43. Chen J, Guo Y, Zeng W, et al. ER stress triggers MCP-1 expression
through SET7 / 9-induced histone methylation in the
kidneys of db / db mice. Am. J. Physiol. 2014;306:916–925.
- 44. Li Y, Reddy MA, Miao F, et al. Role of the histone H3 lysine 4
methyltransferase, SET7/9, in the regulation of NF-κB-dependent
inflammatory genes: Relevance to diabetes and inflammation.
J. Biol. Chem. 2008;283:26771–26781
- 45. Villeneuve LM, Reddy MA, et al. Epigenetic histone H3 lysine 9
methylation in metabolic memory and inflammatory phenotype
of vascular smooth muscle cells in diabetes. Proc. Natl. Acad.
Sci. 2008;105:9047–9052.
- 46. Jia Y, Reddy MA, Das S, et al. Dysregulation of histone H3 lysine
27 trimethylation in transforming growth factor-β1-induced
gene expression in mesangial cells and diabetic kidney. J. Biol.
Chem. 2019;294:12695–12707.
- 47. Lin SH, Ho WT, Wang YT, et al. Histone methyltransferase
Suv39h1 attenuates high glucose-induced fibronectin
and p21WAF1 in mesangial cells. Int. J. Biochem. Cell Biol.
2016;78:96–105.
- 48. Syreeni A, El-Osta A, Forsblom C, et al. Genetic examination
of SETD7 and SUV39H1/H2 methyltransferases and the risk of
diabetes complications in patients with type 1 diabetes. Diabetes.
2011; 60:3073–3080.
- 49. Bijkerk R, Duijs JMGJ, Khairoun M, et al. Circulating MicroRNAs
associate with diabetic nephropathy and systemic microvascular
damage and normalize after simultaneous pancreas-kidney
transplantation. Am. J. Transplant. 2015;15:1081–1090.
- 50. Assmann TS, Recamonde-Mendoza M, Costa AR, et al. Circulating miRNAs in diabetic kidney disease: Case–control study
and in silico analyses. Acta Diabetol. 2019;56:55–65.
- 51. Zampetaki A, Willeit P, Burr S, et al. Angiogenic microRNAs
linked to incidence and progression of diabetic retinopathy in
type 1 diabetes. Diabetes. 2016;65:216–227.
- 52. Santos-Bezerra DP, Santos AS, Guimarães, GC, et al. Micro-RNAs
518d-3p and 618 are upregulated in individuals with type
1 diabetes with multiple microvascular complications. Front.
Endocrinol. 2019;10:385.
- 53. Bera A, Das F, Ghosh-Choudhury N, Mariappan MM, Kasinath
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