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Thioredoxin-Interacting Protein Inhibited Vascular Endothelial Cell–Induced HREC Angiogenesis Treatment of Diabetic Retinopathy

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Abstract

Diabetic retinopathy is the most common reason for blindness among employed adults worldwide. Hyperglycemia and the overaccumulation of vascular endothelial growth factor (VEGF) lead to diabetic retinopathy, pathological angiogenesis in diabetic retinopathy, and consequent visual impairment. Expression levels of thioredoxin-interacting protein (TXNIP) substantially increase in retinal endothelial cells in diabetic circumstances. The part of TXNIP in retinal angiogenesis combined with diabetes remains unclear. This study examined the effect of reduced TXNIP expression levels and determined how it affects diabetic retinal angiogenesis. Display of human retinal vascular endothelial cells (HRECs) to moderately high glucose (MHG) encouraged tube formation and cell migration, not cell proliferation. In response to MHG conditions, in HRECs, TXNIP knockdown inhibited the production of reactive oxygen species (ROS), cell migration, tube formation, and the Akt/mTOR activation pathway. In addition, gene silencing of TXNIP decreased the VEGF-triggered angiogenic response in HRECs by preventing activation of both VEGF receptor 2 and the downstream components of the Akt/mTOR pathway signaling. Furthermore, TXNIP knockout mice reduced VEGF-induced or VEGF- and MHG-triggered ex vivo retinal angiogenesis compared to wild-type mice. Finally, our findings revealed that TXNIP knockdown suppressed VEGF- and MHG-triggered angiogenic responses in HRECs and mouse retinas, indicating that TXNIP is a promising therapeutic window against the proliferation of diabetic patients’ retinopathy.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on request.

References

  1. Mariadoss, A. V. A., Sivakumar, A. S., Lee, C.-H., & S.J. (2022). Kim, Diabetes mellitus and diabetic foot ulcer: Etiology, biochemical and molecular based treatment strategies via gene and nanotherapy. Biomedicine & Pharmacotherapy, 151, 113134. https://doi.org/10.1016/j.biopha.2022.113134

    Article  CAS  Google Scholar 

  2. Bourne, R. R. A., Stevens, G. A., White, R. A., Smith, J. L., Flaxman, S. R., Price, H., Jonas, J. B., Keeffe, J., Leasher, J., & Naidoo, K. (2013). Causes of vision loss worldwide, 1990–2010: A systematic analysis, Lancet. Global Health, 1, e339–e349.

    Google Scholar 

  3. Arnaoutova, I., George, J., Kleinman, H. K., & Benton, G. (2009). The endothelial cell tube formation assay on basement membrane turns 20: State of the science and the art. Angiogenesis, 12, 267–274.

    Article  Google Scholar 

  4. Shin-Young, P., Xi, S., Jinjiang, P., Chen, Y., & B.B. C. (2013). Thioredoxin-interacting protein mediates sustained VEGFR2 signaling in endothelial cells required for angiogenesis. Arteriosclerosis Thrombosis and Vascular Biology, 33, 737–743. https://doi.org/10.1161/ATVBAHA.112.300386

    Article  CAS  Google Scholar 

  5. Osaadon, P., Fagan, X. J., Lifshitz, T., & Levy, J. (2014). A review of anti-VEGF agents for proliferative diabetic retinopathy. Eye, 28, 510–520. https://doi.org/10.1038/eye.2014.13

    Article  CAS  Google Scholar 

  6. Primiceri, E., Chiriacò, M. S., Dioguardi, F., Monteduro, A. G., D’Amone, E., Rinaldi, R., Giannelli, G., & Maruccio, G. (2011). Automatic Transwell assay by an EIS cell chip to monitor cell migration. Lab on a Chip, 11, 4081–4086.

    Article  CAS  Google Scholar 

  7. Brackenbury, W. J., & Djamgoz, M. B. A. (2007). Nerve growth factor enhances voltage-gated Na+ channel activity and Transwell migration in Mat-LyLu rat prostate cancer cell line. Journal of Cellular Physiology, 210, 602–608.

    Article  CAS  Google Scholar 

  8. Singh, L.P. (2013). Thioredoxin interacting protein (TXNIP) and pathogenesis of diabetic retinopathy. J Clin Exp Ophthalmo l, 4

  9. Jiang, Y., Leung, A. W., Hua, H., Rao, X., & Xu, C. (2014). Photodynamic action of LED-activated curcumin against Staphylococcus aureus involving intracellular ROS increase and membrane damage. International Journal of Photoenergy, 2014, 637601. https://doi.org/10.1155/2014/637601

    Article  CAS  Google Scholar 

  10. Scimone, C., Alibrandi, S., Scalinci, S. Z., Trovato Battagliola, E., D’Angelo, R., Sidoti, A., & Donato, L. (2020). Expression of pro-angiogenic markers is enhanced by blue light in human RPE cells. Antioxidants (Basel Switzerland), 9, 1154. https://doi.org/10.3390/antiox9111154

    Article  CAS  Google Scholar 

  11. Donato, L., Scimone, C., Alibrandi, S., Abdalla, E. M., Nabil, K. M., D’Angelo, R., & Sidoti, A. (2020). New omics-derived perspectives on retinal dystrophies: Could ion channels-encoding or related genes act as modifier of pathological phenotype? International Journal of Molecular Sciences, 22, 70. https://doi.org/10.3390/ijms22010070

    Article  CAS  Google Scholar 

  12. Donato, L., Abdalla, E. M., Scimone, C., Alibrandi, S., Rinaldi, C., Nabil, K. M., D’Angelo, R., & Sidoti, A. (2021). Impairments of photoreceptor outer segments renewal and phototransduction due to a peripherin rare haplotype variant: Insights from molecular modeling. International Journal of Molecular Sciences, 22, 3484. https://doi.org/10.3390/ijms22073484

    Article  CAS  Google Scholar 

  13. Scimone, C., Donato, L., Alibrandi, S., Vadalà, M., Giglia, G., Sidoti, A., & D’Angelo, R. (2021). N-Retinylidene-N-retinylethanolamine adduct induces expression of chronic inflammation cytokines in retinal pigment epithelium cells. Experimental Eye Research, 209, 108641. https://doi.org/10.1016/j.exer.2021.108641

    Article  CAS  Google Scholar 

  14. Perrone, L., Devi, T. S., Hosoya, K. I., Terasaki, T., & Singh, L. P. (2010). Inhibition of TXNIP expression in vivo blocks early pathologies of diabetic retinopathy. Cell Death & Disease, 1, e65–e65.

    Article  CAS  Google Scholar 

  15. Huang, Q., & Sheibani, N. (2008). High glucose promotes retinal endothelial cell migration through activation of Src, PI3K/Akt1/eNOS, and ERKs. American Journal of Physiology-Regulatory, 295, C1647–C1657.

    Article  CAS  Google Scholar 

  16. Takeuchi, K., Yanai, R., Kumase, F., Morizane, Y., Suzuki, J., Kayama, M., Brodowska, K., Nakazawa, M., Miller, J. W., Connor, K. M., & Vavvas, D. G. (2014). EGF-like-domain-7 is required for VEGF-induced Akt/ERK activation and vascular tube formation in an ex vivo angiogenesis assay. PLoS ONE, 9, e91849. https://doi.org/10.1371/journal.pone.0091849

    Article  CAS  Google Scholar 

  17. White, N. H., Sun, W., & Cleary, P. A. (2008). Diabetes Control and Complications/Epidemiology of Diabetes Interventions and Complications Research Group. Prolonged effect of intensive therapy on the risk of retinopathy complications in patients with type 1 diabetes mellitus: 10 years after the Diabet. Arch Ophthalmology, 126, 1707–1715.

    Article  Google Scholar 

  18. Hammes, H.-P., Du, X., Edelstein, D., Taguchi, T., Matsumura, T., Ju, Q., Lin, J., Bierhaus, A., Nawroth, P., & Hannak, D. (2003). Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental diabetic retinopathy. Nature Medicine, 9, 294–299.

    Article  CAS  Google Scholar 

  19. DeCicco-Skinner, K.L., Henry, G.H., Cataisson, C., Tabib, T., Gwilliam, J.C., Watson, N.J., Bullwinkle, E.M., Falkenburg, L., O’Neill, R.C., Morin, A. (2014). Endothelial cell tube formation assay for the in vitro study of angiogenesis, JoVE Journal of Vis Exp, e51312.

  20. Brownlee, M. (2005). The pathobiology of diabetic complications. Diabetes, 54, 1615–1625. https://doi.org/10.2337/diabetes.54.6.1615

    Article  CAS  Google Scholar 

  21. Kowluru, R.A., Chan, P.-S. (2007). Oxidative stress and diabetic retinopathy. Exp Diabetes Research, 2007

  22. Al-Shabrawey, M., Rojas, M., Sanders, T., Behzadian, A., El-Remessy, A., Bartoli, M., Parpia, A. K., Liou, G., & Caldwell, R. B. (2008). Role of NADPH oxidase in retinal vascular inflammation. Investigative Ophthalmology & Visual Science, 49, 3239–3244. https://doi.org/10.1167/iovs.08-1755

    Article  Google Scholar 

  23. Park, S.-Y., Shi, X., Pang, J., Yan, C., & Berk, B. C. (2013). Thioredoxin-interacting protein mediates sustained VEGFR2 signaling in endothelial cells required for angiogenesis. Arteriosclerosis Thrombosis and Vascular Biology, 33, 737–743.

    Article  CAS  Google Scholar 

  24. Lv, J., Ma, L., Chen, X., Huang, X., & Wang, Q. (2014). Downregulation of LncRNAH19 and MiR-675 promotes migration and invasion of human hepatocellular carcinoma cells through AKT/GSK-3β/Cdc25A signaling pathway. Journal of Huazhong University of Science and Technology, 34, 363–369.

    Article  CAS  Google Scholar 

  25. Karar, J. A. (2011). Maity, PI3K/AKT/mTOR pathway in angiogenesis. Frontiers in Molecular Neuroscience, 2(4), 51. https://doi.org/10.3389/fnmol.2011.00051.

  26. Mohamed Kasim, M. S., Sundar, S., & Rengan, R. (2018). Synthesis and structure of new binuclear ruthenium(II) arene benzil bis(benzoylhydrazone) complexes: Investigation on antiproliferative activity and apoptosis induction. Inorganic Chemistry Frontiers, 5, 585–596. https://doi.org/10.1039/c7qi00761b

    Article  CAS  Google Scholar 

  27. Mohan, N., Mohamed Subarkhan, M.K., Ramesh, R. (2018). Synthesis, antiproliferative activity and apoptosis-promoting effects of arene ruthenium(II) complexes with N, O chelating ligands. Journal of Organometallic Chemistry, 859. https://doi.org/10.1016/j.jorganchem.2018.01.022.

  28. Mohamed Subarkhan, M.K., Ramesh, R., Liu, Y. (2016). Synthesis and molecular structure of arene ruthenium(II) benzhydrazone complexes: Impact of substitution at the chelating ligand and arene moiety on antiproliferative activity. New Journal of Chemistry, 40. https://doi.org/10.1039/c6nj01936f.

  29. Subarkhan, M. K. M., & Ramesh, R. (2016). Ruthenium(II) arene complexes containing benzhydrazone ligands: Synthesis, structure and antiproliferative activity. Inorganic Chemistry Frontiers, 3, 1245–1255. https://doi.org/10.1039/c6qi00197a

    Article  CAS  Google Scholar 

  30. Mohamed Subarkhan, M., Prabhu, R. N., Raj Kumar, R., & Ramesh, R. (2016). Antiproliferative activity of cationic and neutral thiosemicarbazone copper(ii) complexes. RSC Advances, 6, 25082–25093. https://doi.org/10.1039/C5RA26071J

    Article  CAS  Google Scholar 

  31. Sathiya Kamatchi, T., Mohamed Subarkhan, M. K., Ramesh, R., Wang, H., & Małecki, J. G. (2020). Investigation into antiproliferative activity and apoptosis mechanism of new arene Ru(ii) carbazole-based hydrazone complexes. Dalton Transactions, 49, 11385–11395. https://doi.org/10.1039/D0DT01476A

    Article  CAS  Google Scholar 

  32. Abdelsaid, M. A., & El-Remessy, A. B. (2012). S-glutathionylation of LMW-PTP regulates VEGF-mediated FAK activation and endothelial cell migration. Journal of Cell Science, 125, 4751–4760. https://doi.org/10.1242/jcs.103481

    Article  CAS  Google Scholar 

  33. World C., Spindel, O.N., Berk, B.C (2011). Thioredoxin-interacting protein mediates TRX1 translocation to the plasma membrane in response to tumor necrosis factor-α: A key mechanism for vascular endothelial growth factor receptor-2 transactivation by reactive oxygen species Arterioscler. Thrombosis, and Vascular Biology, 31, 1890 1897

  34. S.O. N., Y. Chen, B.B. C. (2012). Thioredoxin-interacting protein mediates nuclear–to–plasma membrane communication. ArteriosclerosisThrombosis and Vascular Biology, 32, 1264–1270. https://doi.org/10.1161/ATVBAHA.111.244681

  35. Duan, J., Du, C., Shi, Y., Liu, D., & Ma, J. (2018). Thioredoxin-interacting protein deficiency ameliorates diabetic retinal angiogenesis. International Journal of Biochemistry & Cell Biology, 94, 61–70. https://doi.org/10.1016/j.biocel.2017.11.013

    Article  CAS  Google Scholar 

  36. Li, K. G., Chen, J. T., Bai, S. S., Wen, X., Song, S. Y., Yu, Q., Li, J., & Wang, Y. Q. (2009). Intracellular oxidative stress and cadmium ions release induce cytotoxicity of unmodified cadmium sulfide quantum dots. Toxicol Vitr, 23, 1007–1013. https://doi.org/10.1016/j.tiv.2009.06.020

    Article  CAS  Google Scholar 

  37. Devi, T. S., Lee, I., Hüttemann, M., Kumar, A., Nantwi, K. D., & Singh, L. P. (2012). TXNIP links innate host defense mechanisms to oxidative stress and inflammation in retinal Muller glia under chronic hyperglycemia: Implications for diabetic retinopathy. Experimental Diabetes Research, 2012, 438238. https://doi.org/10.1155/2012/438238

    Article  CAS  Google Scholar 

  38. Kovacs, D., Raffa, S., Flori, E., Aspite, N., Briganti, S., Cardinali, G., Torrisi, M. R., & Picardo, M. (2009). Keratinocyte growth factor down-regulates intracellular ROS production induced by UVB. Journal of Dermatological Science, 54, 106–113. https://doi.org/10.1016/j.jdermsci.2009.01.005

    Article  CAS  Google Scholar 

  39. Justus, C.R., Leffler, N., Ruiz-Echevarria, M. L., Yang, V. (2014). In vitro cell migration and invasion assays. Journal of Visualized Experiments, e51046.

  40. Perrone, L., Devi, T. S., Hosoya, K., Terasaki, T., & Singh, L. P. (2009). Thioredoxin interacting protein (TXNIP) induces inflammation through chromatin modification in retinal capillary endothelial cells under diabetic conditions. Journal of Cellular Physiology, 221, 262–272.

    Article  CAS  Google Scholar 

  41. Chen, M., Curtis, T. M., & Stitt, A. W. (2013). Advanced glycation end products and diabetic retinopathy. Current Medicinal Chemistry, 20, 3234–3240.

    Article  CAS  Google Scholar 

  42. Costa, P. Z., & Soares, R. (2013). Neovascularization in diabetes and its complications Unraveling the angiogenic paradox. Life Sciences, 92, 1037–1045. https://doi.org/10.1016/j.lfs.2013.04.001

    Article  CAS  Google Scholar 

  43. Wells, J. A., Glassman, A. R., Ayala, A. R., Jampol, L. M., Aiello, L. P., Antoszyk, A. N., Arnold-Bush, B., Baker, C. W., Bressler, N. M., & Browning, D. J. (2015). Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. New England Journal of Medicine, 372, 1193–1203.

    Article  CAS  Google Scholar 

  44. Du, C., Wu, M., Liu, H., Ren, Y., Du, Y., Wu, H., Wei, J., Liu, C., Yao, F., & Wang, H. (2016). Thioredoxin-interacting protein regulates lipid metabolism via Akt/mTOR pathway in diabetic kidney disease. International Journal of Biochemistry & Cell Biology, 79, 1–13.

    Article  CAS  Google Scholar 

  45. Dunn, L. L., Simpson, P. J. L., Prosser, H. C., Lecce, L., Yuen, G. S. C., Buckle, A., Sieveking, D. P., Vanags, L. Z., Lim, P. R., Chow, R. W. Y., Lam, Y. T., Clayton, Z., Bao, S., Davies, M. J., Stadler, N., Celermajer, D. S., Stocker, R., Bursill, C. A., Cooke, J. P., & Ng, M. K. C. (2014). A critical role for thioredoxin-interacting protein in diabetes-related impairment of angiogenesis. Diabetes, 63, 675–687. https://doi.org/10.2337/db13-0417

    Article  CAS  Google Scholar 

  46. Li, Z., Li, N., Wu, M., Li, X., Luo, Z., & Wang, X. (2013). Expression of miR-126 suppresses migration and invasion of colon cancer cells by targeting CXCR4. Molecular and Cellular Biochemistry, 381, 233–242.

    Article  CAS  Google Scholar 

  47. Shao, Z., Friedlander, M., Hurst, C. G., Cui, Z., Pei, D. T., Evans, L. P., Juan, A. M., Tahir, H., Duhamel, F., Chen, J., Sapieha, P., Chemtob, S., Joyal, J.-S., & Smith, L. E. H. (2013). Choroid sprouting assay: An ex vivo model of microvascular angiogenesis. PLoS ONE, 8, e69552. https://doi.org/10.1371/journal.pone.0069552

    Article  CAS  Google Scholar 

  48. Aplin, A. C., Fogel, E., Zorzi, P., & Nicosia, R. F. (2008). The aortic ring model of angiogenesis. Methods in Enzymology, 443, 119–136.

    Article  CAS  Google Scholar 

  49. Blacher, S., Devy, L., Burbridge, M. F., Roland, G., Tucker, G., Noël, A., & Foidart, J.-M. (2001). Improved quantification of angiogenesis in the rat aortic ring assay. Angiogenesis, 4, 133–142.

    Article  CAS  Google Scholar 

  50. Blatt, R. J., Clark, A. N., Courtney, J., Tully, C., & Tucker, A. L. (2004). Automated quantitative analysis of angiogenesis in the rat aorta model using Image-Pro Plus 41. Comput Methods Programs Biomed, 75, 75–79.

    Article  Google Scholar 

  51. Boettcher, M., Gloe, T., & de Wit, C. (2010). Semiautomatic quantification of angiogenesis. Journal of Surgical Research, 162, 132–139. https://doi.org/10.1016/j.jss.2008.12.009

    Article  Google Scholar 

  52. Cameron, W., N, S.O., C, B.B. (2011). Thioredoxin-interacting protein mediates TRX1 translocation to the plasma membrane in response to tumor necrosis factor-α. Arteriosclerosis, Thrombosis, and Vascular Biology, 31, 1890–1897. https://doi.org/10.1161/ATVBAHA.111.226340

  53. Rezzola, S., Belleri, M., Gariano, G., Ribatti, D., Costagliola, C., Semeraro, F., & Presta, M. (2014). In vitro and ex vivo retina angiogenesis assays. Angiogenesis, 17, 429–442. https://doi.org/10.1007/s10456-013-9398-x

    Article  CAS  Google Scholar 

  54. Patel, H., Chen, J., Das, K. C., & Kavdia, M. (2013). Hyperglycemia induces differential change in oxidative stress at gene expression and functional levels in HUVEC and HMVEC. Cardiovascular Diabetology, 12, 142. https://doi.org/10.1186/1475-2840-12-142

    Article  CAS  Google Scholar 

  55. Brownlee, M. (2005). The pathobiology of diabetic complications: A unifying mechanism. Diabetes, 54, 1615–1625.

    Article  CAS  Google Scholar 

  56. Liu, Z., Yu, E., Liu, W., Liu, X., Tang, S., & Zhu, B. (2014). Translocation of protein kinase C δ contributes to the moderately high glucose-, but not hypoxia-induced proliferation in primary cultured human retinal endothelial cells. Molecular Medicine Reports, 9, 1780–1786.

    Article  CAS  Google Scholar 

  57. Francescone III, R.A., Faibish, M., Shao, R. (2011). A Matrigel-based tube formation assay to assess the vasculogenic activity of tumor cells. Journal of Vis Exp, e3040.

  58. Wang, J., Xu, X., Elliott, M. H., Zhu, M., & Le, Y.-Z. (2010). Müller cell-derived VEGF is essential for diabetes-induced retinal inflammation and vascular leakage. Diabetes, 59, 2297–2305. https://doi.org/10.2337/db09-1420

    Article  CAS  Google Scholar 

  59. Busik, J. V., Mohr, S., & Grant, M. B. (2008). Grant, Hyperglycemia-induced reactive oxygen species toxicity to endothelial cells is dependent on paracrine mediators. Diabetes, 57, 1952–1965. https://doi.org/10.2337/db07-1520

    Article  CAS  Google Scholar 

  60. Chen, H.C. (2005). Boyden chamber assay. Cell Migr, 15–22.

  61. Rinaldi, C., Bramanti, P., Scimone, C., Donato, L., Alafaci, C., D’Angelo, R., & Sidoti, A. (2017). Relevance of CCM gene polymorphisms for clinical management of sporadic cerebral cavernous malformations. Journal of the Neurological Sciences, 380, 31–37. https://doi.org/10.1016/j.jns.2017.06.043

    Article  CAS  Google Scholar 

  62. Scimone, C., Bramanti, P., Ruggeri, A., Katsarou, Z., Donato, L., Sidoti, A., & D’Angelo, R. (2015). Detection of novel mutation in Ccm3 causes familial cerebral cavernous malformations. Journal of Molecular Neuroscience, 57, 400–403. https://doi.org/10.1007/s12031-015-0606-6

    Article  CAS  Google Scholar 

  63. Scimone, C., Donato, L., Katsarou, Z., Bostantjopoulou, S., D’Angelo, R., & Sidoti, A. (2018). Two novel KRIT1 and CCM2 mutations in patients affected by cerebral cavernous malformations: New information on CCM2 penetrance. Frontiers in Neurology, 9, 953. https://doi.org/10.3389/fneur.2018.00953

    Article  Google Scholar 

  64. Scimone, C., Bramanti, P., Ruggeri, A., Donato, L., Alafaci, C., Crisafulli, C., Mucciardi, M., Rinaldi, C., Sidoti, A., & D’Angelo, R. (2016). CCM3/SERPINI1 bidirectional promoter variants in patients with cerebral cavernous malformations: A molecular and functional study. BMC Medical Genetics, 17, 74. https://doi.org/10.1186/s12881-016-0332-0

    Article  CAS  Google Scholar 

  65. Chen, H., Ji, Y., Yan, X., Su, G., Chen, L., & Xiao, J. (2018). Berberine attenuates apoptosis in rat retinal Müller cells stimulated with high glucose via enhancing autophagy and the AMPK/mTOR signaling. Biomedicine & Pharmacotherapy, 108, 1201–1207. https://doi.org/10.1016/j.biopha.2018.09.140

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Ophthalmology Department, Guangdong Province, Longgang District Central Hospital of Shenzhen, Shenzhen, 518117, China

    Jian Yan, Jiantao Deng, Fang Cheng, Tao Zhang, Yixuan Deng & Yulian Cai

  2. Department of Neurology, Guangdong Province, Longgang District Central Hospital, Longgang Road, Shenzhen, 6082518117, No, China

    Wendong Cong

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Dr. Jian Yan, Dr. Jiantao Deng, Dr. Fang Cheng, Dr. Tao Zhang, Dr. Yixuan Deng, and Dr. Yulian Cai supported synthesis, characterization, molecular and biochemical analysis, data curation, formal analysis, and validation. Prof. Wendong Cong helped with supervising the research.

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Yan, J., Deng, J., Cheng, F. et al. Thioredoxin-Interacting Protein Inhibited Vascular Endothelial Cell–Induced HREC Angiogenesis Treatment of Diabetic Retinopathy. Appl Biochem Biotechnol 195, 1268–1283 (2023). https://doi.org/10.1007/s12010-022-04191-1

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