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Graefe's Archive for Clinical and Experimental Ophthalmology

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27-06-2023 | Diabetic Retinopathy | Basic Science

TRIM25 inhibition attenuates inflammation, senescence, and oxidative stress in microvascular endothelial cells induced by hyperglycemia

Authors: Dandan Sun, Shenping Li, Shimei Chen, Shuchang Zhang, Qing Gu, Yinchen Shen, Fang Wei, Ning Wang

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 1/2024

Abstract

Purposes

This work aimed to assess the possible role of TRIM25 in regulating hyperglycemia-induced inflammation, senescence, and oxidative stress in retinal microvascular endothelial cells, all of which exert critical roles in the pathological process of diabetic retinopathy.

Methods

The effects of TRIM25 were investigated using streptozotocin-induced diabetic mice, human primary retinal microvascular endothelial cells cultured in high glucose, and adenoviruses for TRIM25 knockdown and overexpression. TRIM25 expression was evaluated by western blot and immunofluorescence staining. Inflammatory cytokines were detected by western blot and quantitative real-time PCR. Cellular senescence level was assessed by detecting senescent marker p21 and senescence‐associated‐β‐galactosidase activity. The oxidative stress state was accessed by detecting reactive oxygen species and mitochondrial superoxide dismutase.

Results

TRIM25 expression is elevated in the endothelial cells of the retinal fibrovascular membrane from diabetic patients compared with that of the macular epiretinal membrane from non-diabetic patients. Moreover, we have also observed a significant increase in TRIM25 expression in diabetic mouse retina and retinal microvascular endothelial cells under hyperglycemia. TRIM25 knockdown suppressed hyperglycemia-induced inflammation, senescence, and oxidative stress in human primary retinal microvascular endothelial cells while TRIM25 overexpression further aggregates those injuries. Further investigation revealed that TRIM25 promoted the inflammatory responses mediated by the TNF-α/NF-κB pathway and TRIM25 knockdown improved cellular senescence by increasing SIRT3. However, TRIM25 knockdown alleviated the oxidative stress independent of both SIRT3 and mitochondrial biogenesis.

Conclusion

Our study proposed TRIM25 as a potential therapeutic target for the protection of microvascular function during the progression of diabetic retinopathy.

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Antonetti DA, Klein R, Gardner TW (2012) Diabetic retinopathy. N Engl J Med 366(13):1227–1239. https://doi.org/10.1056/NEJMra1005073CrossRefPubMed

Teo ZL, Tham YC, Yu M et al (2021) Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis. Ophthalmology 128(11):1580–1591. https://doi.org/10.1016/j.ophtha.2021.04.027CrossRefPubMed

Hammes HP (2018) Diabetic retinopathy: hyperglycaemia, oxidative stress and beyond. Diabetologia 61(1):29–38. https://doi.org/10.1007/s00125-017-4435-8CrossRefPubMed

Baker RG, Hayden MS, Ghosh S (2011) NF-κB, inflammation, and metabolic disease. Cell Metab 13(1):11–22. https://doi.org/10.1016/j.cmet.2010.12.008CrossRefPubMedPubMedCentral

Dammak A, Huete-Toral F, Carpena-Torres C, et al. (2021) From oxidative stress to inflammation in the posterior ocular diseases: diagnosis and treatment. Pharmaceutics 13(9). https://doi.org/10.3390/pharmaceutics13091376

Di Micco R, Krizhanovsky V, Baker D et al (2021) Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat Rev Mol Cell Biol 22(2):75–95. https://doi.org/10.1038/s41580-020-00314-wCrossRefPubMed

Sabbatinelli J, Prattichizzo F, Olivieri F et al (2019) Where metabolism meets senescence: focus on endothelial cells. Front Physiol 10:1523. https://doi.org/10.3389/fphys.2019.01523CrossRefPubMedPubMedCentral

Giacco F, Brownlee M (2010) Oxidative stress and diabetic complications. Circ Res 107(9):1058–1070. https://doi.org/10.1161/circresaha.110.223545CrossRefPubMedPubMedCentral

Kowluru RA, Chan PS (2007) Oxidative stress and diabetic retinopathy. Exp Diabetes Res 2007:43603. https://doi.org/10.1155/2007/43603CrossRefPubMedPubMedCentral

10.

Heikel G, Choudhury NR, Michlewski G (2016) The role of Trim25 in development, disease and RNA metabolism. Biochem Soc Trans 44(4):1045–1050. https://doi.org/10.1042/bst20160077CrossRefPubMed

11.

Lee JM, Choi SS, Lee YH et al (2018) The E3 ubiquitin ligase TRIM25 regulates adipocyte differentiation via proteasome-mediated degradation of PPARγ. Exp Mol Med 50(10):1–11. https://doi.org/10.1038/s12276-018-0162-6CrossRefPubMedPubMedCentral

12.

Li C, Dou P, Lu X, et al. (2022) Identification and validation of TRIM25 as a glucose metabolism regulator in prostate cancer. International journal of molecular sciences 23(16). https://doi.org/10.3390/ijms23169325

13.

Wan T, Li X, Li Y (2021) The role of TRIM family proteins in autophagy, pyroptosis, and diabetes mellitus. Cell Biol Int 45(5):913–926. https://doi.org/10.1002/cbin.11550CrossRefPubMed

14.

Liu Y, Liu K, Huang Y et al (2020) TRIM25 promotes TNF-α-induced NF-κB activation through potentiating the K63-linked ubiquitination of TRAF2. J Immunol (Baltimore, Md : 1950) 204(6):1499–1507. https://doi.org/10.4049/jimmunol.1900482CrossRef

15.

Park HS, Lu Y, Pandey K et al (2021) NLRP3 inflammasome activation enhanced by TRIM25 is targeted by the NS1 protein of 2009 pandemic influenza a virus. Front Microbiol 12:778950. https://doi.org/10.3389/fmicb.2021.778950CrossRefPubMedPubMedCentral

16.

Crespo-Garcia S, Tsuruda PR, Dejda A et al (2021) Pathological angiogenesis in retinopathy engages cellular senescence and is amenable to therapeutic elimination via BCL-xL inhibition. Cell Metab 33(4):818-832.e817. https://doi.org/10.1016/j.cmet.2021.01.011CrossRefPubMed

17.

Kida Y, Goligorsky MS (2016) Sirtuins, cell senescence, and vascular aging. Can J Cardiol 32(5):634–641. https://doi.org/10.1016/j.cjca.2015.11.022CrossRefPubMed

18.

Chen T, Ma C, Fan G et al (2021) SIRT3 protects endothelial cells from high glucose-induced senescence and dysfunction via the p53 pathway. Life Sci 264:118724. https://doi.org/10.1016/j.lfs.2020.118724CrossRefPubMed

19.

Tang X, Luo YX, Chen HZ et al (2014) Mitochondria, endothelial cell function, and vascular diseases. Front Physiol 5:175. https://doi.org/10.3389/fphys.2014.00175CrossRefPubMedPubMedCentral

20.

Han L, Li J, Li J et al (2020) Activation of AMPK/Sirt3 pathway by phloretin reduces mitochondrial ROS in vascular endothelium by increasing the activity of MnSOD via deacetylation. Food Funct 11(4):3073–3083. https://doi.org/10.1039/c9fo02334hCrossRefPubMed

21.

Chen ML, Zhu XH, Ran L, et al. (2017) Trimethylamine-N-oxide induces vascular inflammation by activating the NLRP3 inflammasome through the SIRT3-SOD2-mtROS signaling pathway. J Am Heart Assoc 6(9). https://doi.org/10.1161/jaha.117.006347

22.

Bagul PK, Katare PB, Bugga P, et al. (2018) SIRT-3 modulation by resveratrol improves mitochondrial oxidative phosphorylation in diabetic heart through deacetylation of TFAM. Cells 7(12). https://doi.org/10.3390/cells7120235

23.

Lee NR, Kim HI, Choi MS et al (2015) Regulation of MDA5-MAVS antiviral signaling axis by TRIM25 through TRAF6-mediated NF-κB activation. Mol Cells 38(9):759–764. https://doi.org/10.14348/molcells.2015.0047CrossRefPubMedPubMedCentral

24.

Mei P, Xie F, Pan J et al (2021) E3 ligase TRIM25 ubiquitinates RIP3 to inhibit TNF induced cell necrosis. Cell Death Differ 28(10):2888–2899. https://doi.org/10.1038/s41418-021-00790-3CrossRefPubMedPubMedCentral

25.

Tian X, Xue Y, Xie G et al (2021) (-)-Epicatechin ameliorates cigarette smoke-induced lung inflammation via inhibiting ROS/NLRP3 inflammasome pathway in rats with COPD. Toxicol Appl Pharmacol 429:115674. https://doi.org/10.1016/j.taap.2021.115674CrossRefPubMed

26.

Ge MX, Shi YK, Liu D (2022) Tripartite motif-containing 25 facilitates immunosuppression and inhibits apoptosis of glioma via activating NF-κB. Exp Biol Med (Maywood) 247(17):1529–1541. https://doi.org/10.1177/15353702221099460CrossRefPubMed

27.

Rufini A, Tucci P, Celardo I et al (2013) Senescence and aging: the critical roles of p53. Oncogene 32(43):5129–5143. https://doi.org/10.1038/onc.2012.640CrossRefPubMed

28.

Vigneron A, Vousden KH (2010) p53, ROS and senescence in the control of aging. Aging 2(8):471–474. https://doi.org/10.18632/aging.100189CrossRefPubMedPubMedCentral

29.

Zhang P, Elabd S, Hammer S et al (2015) TRIM25 has a dual function in the p53/Mdm2 circuit. Oncogene 34(46):5729–5738. https://doi.org/10.1038/onc.2015.21CrossRefPubMed

30.

Chen Y, Zhao Y, Yang X et al (2022) USP44 regulates irradiation-induced DNA double-strand break repair and suppresses tumorigenesis in nasopharyngeal carcinoma. Nat Commun 13(1):501. https://doi.org/10.1038/s41467-022-28158-2CrossRefPubMedPubMedCentral

31.

Nishikawa T, Edelstein D, Du XL et al (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404(6779):787–790. https://doi.org/10.1038/35008121CrossRefPubMed

32.

Mao X, Ji M, Kang L et al (2022) XRCC5 downregulated by TRIM25 is susceptible for lens epithelial cell apoptosis. Cell Signal 94:110314. https://doi.org/10.1016/j.cellsig.2022.110314CrossRefPubMed

33.

Yang X, Zhang F, Liu X et al (2022) FOXO4 mediates resistance to oxidative stress in lens epithelial cells by modulating the TRIM25/Nrf2 signaling. Exp Cell Res 420(1):113340. https://doi.org/10.1016/j.yexcr.2022.113340CrossRefPubMed

34.

Liu Y, Tao S, Liao L et al (2020) TRIM25 promotes the cell survival and growth of hepatocellular carcinoma through targeting Keap1-Nrf2 pathway. Nat Commun 11(1):348. https://doi.org/10.1038/s41467-019-14190-2CrossRefPubMedPubMedCentral

Title: TRIM25 inhibition attenuates inflammation, senescence, and oxidative stress in microvascular endothelial cells induced by hyperglycemia
Authors: Dandan Sun
Shenping Li
Shimei Chen
Shuchang Zhang
Qing Gu
Yinchen Shen
Fang Wei
Ning Wang
Publication date: 27-06-2023
Publisher: Springer Berlin Heidelberg
Keywords: Diabetic Retinopathy
Diabetic Retinopathy
Hyperglycemia
Adenovirus
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 1/2024
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-023-06160-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

TRIM25 inhibition attenuates inflammation, senescence, and oxidative stress in microvascular endothelial cells induced by hyperglycemia

Abstract

Purposes

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purposes

Methods

Results

Conclusion

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