The Role of Endothelial-to-Mesenchymal Transition (EndoMT) in Organ Fibrosis: Research Article

Jian-Guo Xie; Da-Peng Wang

doi:10.58372/2835-6276.1099

Authors

Jian-Guo Xie
Da-Peng Wang

DOI:

https://doi.org/10.58372/2835-6276.1099

Keywords:

EndoMT, fibrosis, TGF-β, Notch, Wnt/β, Catenin

Abstract

Endothelial cells and mesenchymal cells are two distinct cell types that have different forms and functions. A growing number of evidence that endothelial cells could differentiate into myofibroblasts (EndoMT) during the development of organ fibrosis. In this review, we discuss the role of EndoMT in renal fibrosis, cardiac fibrosis and pulmonary fibrosis and summarize representative signaling pathways involved in the process of EndoMT. Understanding the role and mechanisms of EndoMT in organ fibrosis will clear the therapeutic potential of targeting this process.

References

dela Paz NG, D'Amore PA. Arterial versus venous endothelial cells. Cell Tissue Res. 2009;335(1):5-16.

Ishii Y, Langberg J, Rosborough K, Mikawa T. Endothelial cell lineages of the heart. Cell Tissue Res. 2009;335(1):67-73.

Kyuno D, Yamaguchi H, Ito T, et al. Targeting tight junctions during epithelial to mesenchymal transition in human pancreatic cancer. World J Gastroenterol. 2014;20(31):10813-10824.

Somoza RA, Welter JF, Correa D, Caplan AI. Chondrogenic differentiation of mesenchymal stem cells: challenges and unfulfilled expectations. Tissue Eng Part B Rev. 2014;20(6):596-608.

Haynes BA, Yang LF, Huyck RW, et al. Endothelial-to-Mesenchymal Transition in Human Adipose Tissue Vasculature Alters the Particulate Secretome and Induces Endothelial Dysfunction. Arterioscler Thromb Vasc Biol. 2019;39(10):2168-2191.

Greaves D, Calle Y. Epithelial Mesenchymal Transition (EMT) and Associated Invasive Adhesions in Solid and Haematological Tumours. Cells. 2022;11(4):649. Published 2022 Feb 13.

Auersperg N, Pan J, Grove BD, et al. E-cadherin induces mesenchymal-to-epithelial transition in human ovarian surface epithelium. Proc Natl Acad Sci U S A. 1999;96(11):6249-6254.

Chen PY, Qin L, Baeyens N, et al. Endothelial-to-mesenchymal transition drives atherosclerosis progression. J Clin Invest. 2015;125(12):4514-4528.

Boström KI, Yao J, Guihard PJ, Blazquez-Medela AM, Yao Y. Endothelial-mesenchymal transition in atherosclerotic lesion calcification. Atherosclerosis. 2016;253:124-127.

Li Y, Lui KO, Zhou B. Reassessing endothelial-to-mesenchymal transition in cardiovascular diseases. Nat Rev Cardiol. 2018;15(8):445-456.

Li L, Fu H, Liu Y. The fibrogenic niche in kidney fibrosis: components and mechanisms. Nat Rev Nephrol. 2022;18(9):545-557.

Eddy AA. Molecular insights into renal interstitial fibrosis. J Am Soc Nephrol. 1996;7(12):2495-2508.

LeBleu VS, Taduri G, O'Connell J, et al. Origin and function of myofibroblasts in kidney fibrosis. Nat Med. 2013;19(8):1047-1053.

Zeisberg EM, Potenta SE, Sugimoto H, Zeisberg M, Kalluri R. Fibroblasts in kidney fibrosis emerge via endothelial-to-mesenchymal transition. J Am Soc Nephrol. 2008;19(12):2282-2287.

Zeisberg EM, Tarnavski O, Zeisberg M, et al. Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med. 2007;13(8):952-961.

Bischoff J. Endothelial-to-Mesenchymal Transition. Circ Res. 2019;124(8):1163-1165.

Baumann K. Mechanotransduction: Kindlin' the fate of mesenchymal stem cells. Nat Rev Mol Cell Biol. 2018;19(5):278-279.

Peng Q, Shan D, Cui K, et al. The Role of Endothelial-to-Mesenchymal Transition in Cardiovascular Disease. Cells. 2022;11(11):1834.

Gorelova A, Berman M, Al Ghouleh I. Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension. Antioxid Redox Signal. 2021;34(12):891-914.

Hashimoto N, Phan SH, Imaizumi K, et al. Endothelial-mesenchymal transition in bleomycin-induced pulmonary fibrosis. Am J Respir Cell Mol Biol. 2010;43(2):161-172.

Lv Z, Wang Y, Liu YJ, et al. NLRP3 Inflammasome Activation Contributes to Mechanical Stretch-Induced Endothelial-Mesenchymal Transition and Pulmonary Fibrosis. Crit Care Med. 2018;46(1):e49-e58.

Ma J, van der Zon G, Gonçalves MAFV, et al. TGF-β-Induced Endothelial to Mesenchymal Transition Is Determined by a Balance Between SNAIL and ID Factors. Front Cell Dev Biol. 2021;9:616610.

Tzavlaki K, Moustakas A. TGF-β Signaling. Biomolecules. 2020;10(3):487.

Li Y, Lui KO, Zhou B. Reassessing endothelial-to-mesenchymal transition in cardiovascular diseases. Nat Rev Cardiol. 2018;15(8):445-456.

Fan M, Yang K, Wang X, et al. Lactate promotes endothelial-to-mesenchymal transition via Snail1 lactylation after myocardial infarction. Sci Adv. 2023;9(5):eadc9465.

Piera-Velazquez S, Mendoza FA, Jimenez SA. Endothelial to Mesenchymal Transition (EndoMT) in the Pathogenesis of Human Fibrotic Diseases. J Clin Med. 2016;5(4):45. Published 2016 Apr 11.

Pardali E, Sanchez-Duffhues G, Gomez-Puerto MC, Ten Dijke P. TGF-β-Induced Endothelial-Mesenchymal Transition in Fibrotic Diseases. Int J Mol Sci. 2017;18(10):2157.

Cooley BC, Nevado J, Mellad J, et al. TGF-β signaling mediates endothelial-to-mesenchymal transition (EndoMT) during vein graft remodeling. Sci Transl Med. 2014;6(227):227ra34.

Lopez D, Niu G, Huber P, Carter WB. Tumor-induced upregulation of Twist, Snail, and Slug represses the activity of the human VE-cadherin promoter. Arch Biochem Biophys. 2009;482(1-2):77-82.

Zhou F, Wang M, Luo T, Qu J, Chen WR. Photo-activated chemo-immunotherapy for metastatic cancer using a synergistic graphene nanosystem. Biomaterials. 2021;265:120421.

Manetti M, Romano E, Rosa I, et al. Endothelial-to-mesenchymal transition contributes to endothelial dysfunction and dermal fibrosis in systemic sclerosis. Ann Rheum Dis. 2017;76(5):924-934.

Zheng X, Peng M, Li Y, et al. Cathelicidin-related antimicrobial peptide protects against cardiac fibrosis in diabetic mice heart by regulating endothelial-mesenchymal transition. Int J Biol Sci. 2019;15(11):2393-2407.

Zhang Y, Jin D, Kang X, et al. Signaling Pathways Involved in Diabetic Renal Fibrosis. Front Cell Dev Biol. 2021;9:696542. Published 2021 Jul 12. doi:10.3389/fcell.2021.696542

Li L, Zhou G, Fu R, et al. Polysaccharides extracted from balanophora polyandra Griff (BPP) ameliorate renal Fibrosis and EMT via inhibiting the Hedgehog pathway. J Cell Mol Med. 2021;25(6):2828-2840.

Choudhry H, Harris AL. Advances in Hypoxia-Inducible Factor Biology. Cell Metab. 2018;27(2):281-298.

Zou J, Liu Y, Li B, et al. Autophagy attenuates endothelial-to-mesenchymal transition by promoting Snail degradation in human cardiac microvascular endothelial cells. Biosci Rep. 2017;37(5):BSR20171049.

Gong J, Feng Z, Peterson AL, et al. Endothelial to mesenchymal transition during neonatal hyperoxia-induced pulmonary hypertension. J Pathol. 2020;252(4):411-422.

Matsui T, Oda E, Higashimoto Y, Yamagishi S. Glyceraldehyde-derived pyridinium (GLAP) evokes oxidative stress and inflammatory and thrombogenic reactions in endothelial cells via the interaction with RAGE. Cardiovasc Diabetol. 2015;14:1.

Wang B, Li ZL, Zhang YL, Wen Y, Gao YM, Liu BC. Hypoxia and chronic kidney disease. EBioMedicine. 2022;77:103942.

Moonen JR, Lee ES, Schmidt M, et al. Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress. Cardiovasc Res. 2015;108(3):377-386.

Hulshoff MS, Del Monte-Nieto G, Kovacic J, Krenning G. Non-coding RNA in endothelial-to-mesenchymal transition. Cardiovasc Res. 2019;115(12):1716-1731.

Moskalik A, Ratajska A, Majchrzak B, et al. miR-31-5p-Modified RAW 264.7 Macrophages Affect Profibrotic Phenotype of Lymphatic Endothelial Cells In Vitro. Int J Mol Sci. 2022;23(21):13193.

Chen D, Zhang C, Chen J, et al. miRNA-200c-3p promotes endothelial to mesenchymal transition and neointimal hyperplasia in artery bypass grafts. J Pathol. 2021;253(2):209-224.