255
Views
0
CrossRef citations to date
0
Altmetric
Review

The role of the Notch pathway in the pathogenesis of systemic sclerosis: clinical implications

ORCID Icon & ORCID Icon
Pages 1257-1267 | Received 04 Sep 2021, Accepted 27 Oct 2021, Published online: 02 Nov 2021

References

  • Clements PJ, and Furst DE. Systemic sclerosis. 2nd ed. Philadelphia, USA: Lippincott Williams & Wilkins; 2004. ISBN 978-0781737449 .
  • Van PJT, Smith V, Haspeslagh M, et al. Histopathological cutaneous alterations in systemic sclerosis : a clinicopathological study. Arthritis Res Ther. 2011;13(1):R35.
  • Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. NEJM. 2009;360(19):1989–2003.
  • Kavian N, Batteux F. Macro- and microvascular disease in systemic sclerosis. Vasc Pharmacol. 2015;71:16–23.
  • Asano Y, Sato S. Vasculopathy in scleroderma. Semin Immunopathol. 2015;37(5):489–500.
  • Karassa FB, Ioannidis JBA. Mortality in systemic sclerosis. Clin Exp Rheumatol. 2008;26:S85–93.
  • Wei J, Bhattacharyya S, Tourtellotte WG, et al. Fibrosis in systemic sclerosis: emerging concepts and implications for targeted therapy. Autoimmun Rev. 2011;10(5):267–275.
  • Elhai M, Meune C, Avouac J, et al. Trends in mortality in patients with systemic sclerosis over 40 years: a systematic review and meta-analysis of cohort studies. Rheumatol (United Kingdom). 2012;51:1017–1026.
  • Takahashi Y, Inoue T, Gossler A, et al. Feedback loops comprising Dll1, Dll3 and Mesp2, and differential involvement of Psen1 are essential for rostrocaudal patterning of somites. Development 2003;130(18):4259–4268.
  • Lai EC. Notch signaling: control of cell communication and cell fate. Development 2004;131(5):965–973.
  • Chillakuri CR, Sheppard D, Lea SM, et al. Notch receptor-ligand binding and activation: insights from molecular studies. Semin Cell Dev Biol. 2012;23(4):421–428.
  • Gordon WR, Arnett KL, Blacklow SC. The molecular logic of Notch signaling–a structural and biochemical perspective. J Cell Sci. 2008;121(19):3109–3119.
  • Iso T, Kedes L, Hamamori Y. HES and HERP families: multiple effectors of the Notch signaling pathway. J Cell Physiol. 2003;194(3):237–255.
  • Ayaz F, Osborne BA. Non-canonical Notch signaling in cancer and immunity. Front Oncol. 2014;4:1–6.
  • Andersen P, Uosaki H, Shenje L, et al. Non-canonical Notch signaling: emerging role and mechanism. Natl Institutes Heal. 2013;22:257–265.
  • Layden MJ, Martindale MQ. Non-canonical Notch signaling represents an ancestral mechanism to regulate neural differentiation. Evodevo. 2014;5(1):30.
  • Jin S, Mutvei AP, Chivukula IV, et al. Non-canonical Notch signaling activates IL-6/JAK/STAT signaling in breast tumor cells and is controlled by p53 and IKKα/IKKβ. Oncogene. 2013;32(41):4892–4902.
  • Kopan R. Notch signalling. 1st ed. San Diego, USA: Academic Press, Elsevier; 2010. ISBN 978-0-12-380914-8 .
  • Rockey DC, Bell PD, Hill JA. Fibrosis — a common pathway to organ injury and failure. N Engl J Med. 2015;372(12):1138–1149.
  • Thannickal VJ, Zhou Y, Gaggar A, et al. Fibrosis: ultimate and proximate causes. J Clin Invest. 2014;124(11):4673–4677.
  • Condorelli AG, El HM, and Zambruno G, et al. Notch - ing up knowledge on molecular mechanisms of skin fibrosis : focus on the multifaceted Notch signalling pathway. J Biomed Sci. 2021;28(36):1–17.
  • Zmorzy S, Styk W, Filip AA, et al. The significance of NOTCH pathway in the development of fibrosis in systemic sclerosis. Ann Dermatol. 2019;31(4):365–371.
  • Beyer C, Dees C, Distler JHW. Morphogen pathways as molecular targets for the treatment of fibrosis in systemic sclerosis. Acta Dermatol Res. 2013;305(1):1–8.
  • Hu B, Phan SH. Notch in fibrosis and as a target of anti-fibrotic therapy. Pharmacol Res. 2016;108:57–64.
  • Beyer C, Distler JHW. Morphogen pathways in systemic sclerosis. Curr Rheumatol Rep. 2013;15(1):299.
  • Dees C, Tomcik M, Zerr P, et al. Notch signalling regulates fibroblast activation and collagen release in systemic sclerosis. Ann Rheum Dis. 2011;70(7):1304–1310.
  • Parapuram SK, Shi-Wen X, Elliott C, et al. Loss of PTEN expression by dermal fibroblasts causes skin fibrosis. J Invest Dermatol. 2011;131(10):1996–2003.
  • Bertrand FE, McCubrey JA, Angus CW, et al. NOTCH and PTEN in prostate cancer. Adv Biol Regul. 2014;56:51–65.
  • Kavian N, Servettaz A, Mongaret C, et al. Targeting ADAM-17/notch signaling abrogates the development of systemic sclerosis in a murine model. Arthritis Rheum. 2010;62(11):3477–3487.
  • Meng XM, Nikolic-Paterson DJ, Lan HY. TGF-β: the master regulator of fibrosis. Nat Rev Nephrol. 2016;12(6):325–338.
  • Chen Y, Shi-wen X, and Eastwood M, et al. Contribution of activin receptor – like Kinase 5 (transforming growth factor β receptor type I) signaling to the fibrotic phenotype of scleroderma fibroblasts. Arthritis Rheum. 2006;54(4):1309–1316.
  • Shi-Wen X, Thompson K, Khan K, et al. Focal adhesion kinase and reactive oxygen species contribute to the persistent fibrotic phenotype of lesional scleroderma fibroblasts. Rheumatol (United Kingdom). 2012;51:2146–2154.
  • Leask A. The hard problem: mechanotransduction perpetuates the myofibroblast phenotype in scleroderma fibrosis. Wound Repair Regen. 2021;29(4):582–587.
  • Totaro A, Castellan M, Di BD, et al. Crosstalk between YAP/TAZ and Notch signaling. Trends Cell Biol. 2018;28(7):560–573.
  • Zavadil J, Bitzer M, Liang D, et al. Genetic programs of epithelial cell plasticity directed by transforming growth factor- ␤. PNAS. 2001;98:6686–6691.
  • Blokzijl A, Dahlqvist C, Reissmann E, et al. Cross-talk between the Notch and TGF-beta signaling pathways mediated by interaction of the Notch intracellular domain with Smad3. J Cell Biol. 2003;163(4):723–728.
  • Sirin Y, Susztak K. The role of Notch in the kidney, development and beyond. J Pathol. 2012;226(2):394–403.
  • LaFoya B, Munroe JA, Mia MM, et al. Notch: a multi-functional integrating system of microenvironmental signals. Dev Biol. 2016;418(2):227–241.
  • Hu M, Wu C, and Qu S, et al. Notch signaling regulates col1a1 and col1a2 expression in airway fibroblasts. Exp Biol Med (Maywood). 2014; 239(12) :1589–96. DOI: https://doi.org/10.1177/1535370214538919.
  • Zhu C, Kim K, Wang X, et al. Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis. Sci Transl Med. 2018; 10(468) :1–14. DOI: https://doi.org/10.1126/scitranslmed.aat0344.
  • Syed F, Bayat A. Notch signaling pathway in keloid disease : enhanced fibroblast activity in a Jagged-1 peptide-dependent manner in lesional vs. extralesional fibroblasts. Wound Repair Regen. 2012;20(5):688–706.
  • Id SH, Park J, Qiu C, et al. Jagged1/Notch2 controls kidney fibrosis via Tfam -mediated metabolic reprogramming. PLoS Biol. 2018;16(9):e2005233.
  • Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial–mesenchymal transition. Nat Rev Mol Cell Biol. 2014;15(3):178–196.
  • Lebleu VS, Taduri G, Teng Y, et al. Origin and function of myofibroblasts in kidney fibrosis. Nat Med. 2014;19:1047–1053.
  • Xu H, Zaidi M, Struve J, et al. Abnormal fibrillin-1 expression and chronic oxidative stress mediate endothelial mesenchymal transition in a murine model of systemic sclerosis. Am J Physiol Cell Physiol. 2011;300(3):C550–C556.
  • Kayser C, Fritzler MJ. Autoantibodies in systemic sclerosis: unanswered questions. Front Immunol. 2015;6:2–7.
  • Chang ACY, Fu Y, Garside VC, et al. Notch Initiates the Endothelial-to-mesenchymal transition in the atrioventricular canal through autocrine activation of soluble Guanylyl Cyclase. Dev Cell. 2011;21(2):288–300.
  • Noseda M, McLean G, Niessen K, et al. Notch activation results in phenotypic and functional changes consistent with endothelial-to-mesenchymal transformation. Circ Res. 2004;94(7):910–917.
  • Liu J, Dong F, Jeong J, et al. Constitutively active Notch1 signaling promotes endothelial-mesenchymal transition in a conditional transgenic mouse model. Int J Mol Med. 2014;34(3):669–676.
  • Jimenez SA. Role of endothelial to mesenchymal transition in the pathogenesis of the vascular alterations in systemic sclerosis. ISRN Rheumatol. 2013;2013:835948.
  • Blanco R, Gerhardt H. VEGF and Notch in tip and stalk cell selection. Cold Spring Harb Perspect Med. 2013;3(1):1–19.
  • Gerber HP, Dixit V, Ferrara N. Vascular endothelial growth factor induces expression of the antiapoptotic proteins Bcl-2 and A1 in vascular endothelial cells. J Biol Chem. 1998;273(21):13313–13316.
  • Dvorak HF, Brown LF, Detmar M, et al. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol. 1995;146:1029–1039.
  • Matsumoto T, Bohman S, Dixelius J, et al. VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis. Embo J. 2005;24(13):2342–2353.
  • Karamysheva A. Mechanisms of angiogenesis. Biochem. 2008;73:751–762.
  • Lobov IB, Renard RA, Papadopoulos N, et al. Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting. Proc Natl Acad Sci U S A. 2007;104(9):3219–3224.
  • Liu Z, Shirakawa T, Li Y, et al. Regulation of Notch1 and Dll4 by vascular endothelial growth factor in arterial endothelial cells : implications for modulating arteriogenesis and angiogenesis regulation of Notch1 and Dll4 by vascular endothelial growth factor in arterial endothelial cel. Society 2003;23:14–25.
  • Williams CK, Li JL, Murga M, et al. Up-regulation of the Notch ligand Delta-like 4 inhibits VEGF-induced endothelial cell function. Blood 2006;107(3):931–939.
  • Funahashi Y, Shawber CJ, Vorontchikhina M, et al. Notch regulates the angiogenic response via induction of VEGFR-1. J Angiogenes Res. 2010;2(1):3.
  • Harrington LS, Sainson RCA, Williams CK, et al. Regulation of multiple angiogenic pathways by Dll4 and Notch in human umbilical vein endothelial cells. Microvasc Res. 2008;75(2):144–154.
  • Agrawal S, Archer C, Schaffer DV. Computational models of the Notch network elucidate mechanisms of context-dependent signaling. PLOS Comput Biol. 2009;5(5):e1000390.
  • Funahashi Y, Shawber CJ, Sharma A, et al. Notch modulates VEGF action in endothelial cells by inducing matrix metalloprotease activity. Vasc Cell. 2011;3(1):2.
  • Hellström M, Phng L-K, Hofmann JJ, et al. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature. 2007;445(7129):776–780.
  • Siekmann AF, Covassin L, Lawson ND. Modulation of VEGF signalling output by the Notch pathway. BioEssays 2008;30(4):303–313.
  • Siekmann AF, Lawson ND. Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries. Nature 2007;445(7129):781–784.
  • Sainson RCA, Harris AL. Regulation of angiogenesis by homotypic and heterotypic notch signalling in endothelial cells and pericytes: from basic research to potential therapies. Angiogenesis. 2008;11(1):41–51.
  • Yang K, Proweller A. Vascular smooth muscle notch signals regulate endothelial cell sensitivity to angiogenic stimulation. J Biol Chem. 2011;286(15):13741–13753.
  • Beets K, Huylebroeck D, Moya IM, et al. Robustness in angiogenesis: notch and BMP shaping waves. Trends Genet. 2013;29(3):140–149.
  • Li JL, Sainson RCA, Shi W, et al. Delta-like 4 Notch Ligand regulates tumor angiogenesis, improves tumor vascular function, and promotes tumor growth in vivo. Cancer Res. 2007;67(23):11244–11253.
  • Patel NS, Li JL, Generali D, et al. Up-regulation of delta-like 4 ligand in human tumor vasculature and the role of basal expression in endothelial cell function. Cancer Res. 2005;65:8690–8697.
  • Huang H. Pericyte-endothelial interactions in the retinal microvasculature. Int J Mol Sci. 2020;21(19):1–18.
  • Hellström M, Gerhardt H, Kalén M, et al. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J Cell Biol. 2001;152:543–553.
  • Cutolo M, Smith V. State of the art on nailfold capillaroscopy: a reliable diagnostic tool and putative biomarker in rheumatology? Rheumatology (Oxford). 2013;52(11):1933–1940.
  • Paula F, Delgado Alves J. Notch signaling in microvascular endothelial cells is modulated by a serum factor in systemic sclerosis. 6th Syst Scler World Congr. Prague, Czech Republic; 2020. p. ID134.
  • Vanderbeck A, Maillard I. Notch signaling at the crossroads of innate and adaptive immunity. J Leukocyte Biol. 2021;109(3):535–548.
  • Seguro Paula F, Ferreira IA, Amaral MC, et al. Systemic sclerosis-related changes on nailfold videocapillaroscopy in genetic and metabolic myopathies. Rheumatol (United Kingdom). 2016;55:1911–1912.
  • Kubo S, Todoroki Y, Nakayamada S, et al. Significance of nailfold videocapillaroscopy in patients with idiopathic inflammatory myopathies. Rheumatol (United Kingdom). 2019;58:120–130.
  • Kontomanolis E, Panteliadou M, Giatromanolaki A, et al. Delta-like ligand 4 (DLL4) in the plasma and neoplastic tissues from breast cancer patients: correlation with metastasis. Med Oncol. 2014;31(5). DOI:https://doi.org/10.1007/s12032-014-0945-0.
  • D’Souza B, Miyamoto A, Weinmaster G. The many facets of Notch ligands. Oncogene. 2008;27(38):5148–5167.
  • Sheldon H, Heikamp E, Turley H, et al. New mechanism for Notch signaling to endothelium at a distance by delta-like 4 incorporation into exosomes. Blood 2010;116(13):2385–2394.
  • Wojcierowska-litwin M, Kowal M, and Michalska-jakubus M, et al. NOTCH3 T6746C and TP53 P72R polymorphisms are associated with the susceptibility to diffuse cutaneous systemic sclerosis. Biomed Res Int. 2020; 2020:1–9. DOI: https://doi.org/10.1155/2020/8465971. Article ID 8465971 .
  • Dees C, Zerr P, Tomcik M, et al. Inhibition of Notch signaling prevents experimental fibrosis and induces regression of established fibrosis. Arthritis Rheum. 2011;63(5):1396–1404.
  • Crabtree JS, Osborne BA, and Miele L. Targeting Notch in oncology: the path forward. Nat Rev Drug Discov. 2021;20(2): 125–44 . DOI: https://doi.org/10.1038/s41573-020-00091-3 .
  • Güner G, Lichtenthaler SF, Dzne D. The substrate repertoire of γ-secretase/presenilin. Semin Cell Dev Biol. 2020;105:27–42.
  • Riccio O, Van GME, Bezdek AC, et al. Loss of intestinal crypt progenitor cells owing to inactivation of both Notch1 and Notch2 is accompanied by derepression of CDK inhibitors p27Kip1 and p57Kip2. EMBO Rep. 2008;9(4):377–383.
  • Moore G, Annett S, and McClements L, et al. Top Notch targeting strategies in cancer: a detailed overview of recent insights and current perspectives. Cells 2020;9(6):1–46.
  • Samon JB, Castillo-martin M, Hadler M, et al. Preclinical analysis of the g -secretase inhibitor PF-03084014 in combination with glucocorticoids in T-cell acute lymphoblastic leukemia. Mol Cancer Ther. 2012;11(7):1565–1576.
  • Keizer RJ, Huitema ADR, Schellens JHM, et al. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010;49(8):493–507.
  • Christopoulos PF, Gjølberg TT, Krüger S, et al. Targeting the Notch signaling pathway in chronic inflammatory diseases. Front Immunol. 2021;12:1–22.
  • Ferrarotto R, Eckhardt G, Patnaik A, et al. A phase I dose-escalation and dose-expansion study of brontictuzumab in subjects with selected solid tumors. Ann Oncol. 2018;29(7):1561–1568.
  • Rosen LS, Wesolowski R, Baffa R, et al. A phase I, dose-escalation study of PF-06650808, an anti-Notch3 antibody–drug conjugate, in patients with breast cancer and other advanced solid tumors. Invest New Drugs. 2020;38(1):120–130.
  • Chiorean EG, LoRusso P, Strother RM, et al. A phase I first-in-human study of enoticumab (REGN421), a fully human delta-like ligand 4 (Dll4) monoclonal antibody in patients with advanced solid tumors. Clin Cancer Res. 2015;21(12):2695–2703.
  • McKeage MJ, Kotasek D, Markman B, et al. Phase IB trial of the anti-cancer stem cell DLL4-binding agent Demcizumab with pemetrexed and carboplatin as first-line treatment of metastatic non-squamous NSCLC. Target Oncol. 2018;13(1):89–98.
  • Masiero M, Li D, Whiteman P, et al. Development of therapeutic anti-Jagged1 antibodies for cancer therapy. Mol Cancer Ther. 2019;18(11):2030–2042.
  • Lafkas D, Shelton A, Chiu C, et al. Therapeutic antibodies reveal Notch control of transdifferentiation in the adult lung. Nature 2015;528(7580):127–131.
  • Rangarajan A, Talora C, Okuyama R, et al. Notch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation. Embo J. 2001;20(13):3427–3436.
  • Distler A, Lang V, Del VT, et al. Combined inhibition of morphogen pathways demonstrates additive anti fi brotic effects and improved tolerability. Ann Rheum Dis. 2014;73(6):1264–1268.
  • Kubo S, Tanaka Y. Scleroderma in an ice-cream shop worker. Rheumatology (Oxford). 2019;58(6):1120–1121.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.