Role of Takeda G Protein‑coupled Receptor 5 in Microvascular Endothelial Cell Dysfunction in Diabetic Retinopathy (Review)

Overview

Journal Exp Ther Med

Specialty Pathology

Date 2022 Oct 14

PMID 36237599

Authors

Miao Zhang

Zhenghao Dong

Wenkang Dong

Dongdong Zhou

Xiang Ren

Affiliations

Soon will be listed here.

Abstract

Diabetic retinopathy (DR) is a frequent microvascular complication of advanced-stage diabetes. Endothelial cell dysfunction (ED) induced by diabetes plays an important role in the development of DR. It is considered that inflammation and mitochondrial homeostasis are associated with the progression of ED. Takeda G protein-coupled receptor 5 (TGR5) is a membrane receptor for bile acids (BAs) that plays an important role in regulating BA metabolism. Recent studies have shown that TGR5 is involved in regulating various mediators of ED and improving the dysfunction of vascular endothelial cells in DR; however, the exploration of specific related mechanisms remains an active research area in this field, which suggests that TGR5 may be one of the potential targets for the treatment of associated ED in DR. In the present review, the association between TGR5 and mitochondrial homeostasis was investigated. The extent of inflammation in DR-induced ED was assessed to provide possible evidence for the development of targeted therapies against DR.

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References

van Nierop F, Scheltema M, Eggink H, Pols T, Sonne D, Knop F . Clinical relevance of the bile acid receptor TGR5 in metabolism. Lancet Diabetes Endocrinol. 2016; 5(3):224-233. DOI: 10.1016/S2213-8587(16)30155-3. View

Noda K, Nakao S, Ishida S, Ishibashi T . Leukocyte adhesion molecules in diabetic retinopathy. J Ophthalmol. 2011; 2012:279037. PMC: 3216271. DOI: 10.1155/2012/279037. View

Claybaugh T, Decker S, McCall K, Slyvka Y, Steimle J, Wood A . L-Arginine Supplementation in Type II Diabetic Rats Preserves Renal Function and Improves Insulin Sensitivity by Altering the Nitric Oxide Pathway. Int J Endocrinol. 2014; 2014:171546. PMC: 3913451. DOI: 10.1155/2014/171546. View

Meza C, La Favor J, Kim D, Hickner R . Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS?. Int J Mol Sci. 2019; 20(15). PMC: 6696313. DOI: 10.3390/ijms20153775. View

Kowluru R, Mishra M . Regulation of Matrix Metalloproteinase in the Pathogenesis of Diabetic Retinopathy. Prog Mol Biol Transl Sci. 2017; 148:67-85. DOI: 10.1016/bs.pmbts.2017.02.004. View

Tang J, Kern T . Inflammation in diabetic retinopathy. Prog Retin Eye Res. 2011; 30(5):343-58. PMC: 3433044. DOI: 10.1016/j.preteyeres.2011.05.002. View

Bucolo C, Drago F, Maisto R, Romano G, DAgata V, Maugeri G . Curcumin prevents high glucose damage in retinal pigment epithelial cells through ERK1/2-mediated activation of the Nrf2/HO-1 pathway. J Cell Physiol. 2019; 234(10):17295-17304. DOI: 10.1002/jcp.28347. View

Williams R, Airey M, Baxter H, Forrester J, Kennedy-Martin T, Girach A . Epidemiology of diabetic retinopathy and macular oedema: a systematic review. Eye (Lond). 2004; 18(10):963-83. DOI: 10.1038/sj.eye.6701476. View

Huang M, Wei R, Wang Y, Su T, Li P, Chen X . The uremic toxin hippurate promotes endothelial dysfunction via the activation of Drp1-mediated mitochondrial fission. Redox Biol. 2018; 16:303-313. PMC: 5953222. DOI: 10.1016/j.redox.2018.03.010. View

10.

Shutt T, Geoffrion M, Milne R, McBride H . The intracellular redox state is a core determinant of mitochondrial fusion. EMBO Rep. 2012; 13(10):909-15. PMC: 3463964. DOI: 10.1038/embor.2012.128. View

11.

Ferrington D, Fisher C, Kowluru R . Mitochondrial Defects Drive Degenerative Retinal Diseases. Trends Mol Med. 2019; 26(1):105-118. PMC: 6938541. DOI: 10.1016/j.molmed.2019.10.008. View

12.

Rovira-Llopis S, Banuls C, Diaz-Morales N, Hernandez-Mijares A, Rocha M, Victor V . Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications. Redox Biol. 2017; 11:637-645. PMC: 5284490. DOI: 10.1016/j.redox.2017.01.013. View

13.

Moreno A, Lozano M, Salinas P . Diabetic retinopathy. Nutr Hosp. 2013; 28 Suppl 2:53-6. DOI: 10.3305/nh.2013.28.sup2.6714. View

14.

Zhou X, Guan Z, Jin X, Zhao J, Chen G, Ding J . Reversal of alopecia areata, osteoporosis follow treatment with activation of Tgr5 in mice. Biosci Rep. 2021; 41(7). PMC: 8292761. DOI: 10.1042/BSR20210609. View

15.

Mikelis C, Simaan M, Ando K, Fukuhara S, Sakurai A, Amornphimoltham P . RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock. Nat Commun. 2015; 6:6725. PMC: 4394241. DOI: 10.1038/ncomms7725. View

16.

Liang Q, Kobayashi S . Mitochondrial quality control in the diabetic heart. J Mol Cell Cardiol. 2016; 95:57-69. PMC: 6263145. DOI: 10.1016/j.yjmcc.2015.12.025. View

17.

Dicks N, Gutierrez K, Currin L, de Macedo M, Glanzner W, Mondadori R . Tauroursodeoxycholic acid/TGR5 signaling promotes survival and early development of glucose-stressed porcine embryos†. Biol Reprod. 2021; 105(1):76-86. PMC: 8256098. DOI: 10.1093/biolre/ioab072. View

18.

Song J, Li J, Hou F, Wang X, Liu B . Mangiferin inhibits endoplasmic reticulum stress-associated thioredoxin-interacting protein/NLRP3 inflammasome activation with regulation of AMPK in endothelial cells. Metabolism. 2014; 64(3):428-37. DOI: 10.1016/j.metabol.2014.11.008. View

19.

Xiang E, Han B, Zhang Q, Rao W, Wang Z, Chang C . Human umbilical cord-derived mesenchymal stem cells prevent the progression of early diabetic nephropathy through inhibiting inflammation and fibrosis. Stem Cell Res Ther. 2020; 11(1):336. PMC: 7397631. DOI: 10.1186/s13287-020-01852-y. View

20.

Voiosu A, Wiese S, Voiosu T, Bendtsen F, Moller S . Bile acids and cardiovascular function in cirrhosis. Liver Int. 2017; 37(10):1420-1430. DOI: 10.1111/liv.13394. View