218
Views
1
CrossRef citations to date
0
Altmetric
ORIGINAL RESEARCH

Identification and Characterization of a Novel Nanobody Against Human CTGF to Reveal Its Antifibrotic Effect in an in vitro Model of Liver Fibrosis

, , , , , , & show all
Pages 5407-5422 | Received 01 Jul 2023, Accepted 14 Sep 2023, Published online: 21 Sep 2023

References

  • Kisseleva T, Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol. 2021;18(3):151–166. doi:10.1038/s41575-020-00372-7
  • Ding N, Yu RT, Subramaniam N, et al. A vitamin D receptor/SMAD genomic circuit gates hepatic fibrotic response. Cell. 2013;153(3):601–613. doi:10.1016/j.cell.2013.03.028
  • Tsuchida T, Friedman SL. Mechanisms of hepatic stellate cell activation. Nat Rev Gastroenterol Hepatol. 2017;14(7):397–411. doi:10.1038/nrgastro.2017.38
  • Parola M, Pinzani M. Liver fibrosis: pathophysiology, pathogenetic targets and clinical issues. Mol Aspects Med. 2019;65:37–55. doi:10.1016/j.mam.2018.09.002
  • Henderson NC, Rieder F, Wynn TA. Fibrosis: from mechanisms to medicines. Nature. 2020;587(7835):555–566. doi:10.1038/s41586-020-2938-9
  • Wiering L, Subramanian P, Hammerich L. Hepatic stellate cells: dictating outcome in nonalcoholic fatty liver disease. Cell Mol Gastroenterol Hepatol. 2023;15(6):1277–1292. doi:10.1016/j.jcmgh.2023.02.010
  • Dewidar B, Meyer C, Dooley S, Meindl-Beinker AN. TGF-beta in hepatic stellate cell activation and liver fibrogenesis-updated 2019. Cells. 2019;8(11):1419. doi:10.3390/cells8111419
  • Seki E, De Minicis S, Osterreicher CH, et al. TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med. 2007;13(11):1324–1332. doi:10.1038/nm1663
  • Ramazani Y, Knops N, Elmonem MA, et al. Connective tissue growth factor (CTGF) from basics to clinics. Matrix Biol. 2018;68–69:44–66. doi:10.1016/j.matbio.2018.03.007
  • Fabregat I, Moreno-Caceres J, Sanchez A, et al. TGF-beta signalling and liver disease. FEBS J. 2016;283(12):2219–2232. doi:10.1111/febs.13665
  • Wang Q, Usinger W, Nichols B, et al. Cooperative interaction of CTGF and TGF-beta in animal models of fibrotic disease. Fibrogenesis Tissue Repair. 2011;4(1):4. doi:10.1186/1755-1536-4-4
  • Paradis V, Dargere D, Vidaud M, et al. Expression of connective tissue growth factor in experimental rat and human liver fibrosis. Hepatology. 1999;30(4):968–976. doi:10.1002/hep.510300425
  • Williams EJ, Gaca MD, Brigstock DR, Arthur MJ, Benyon RC. Increased expression of connective tissue growth factor in fibrotic human liver and in activated hepatic stellate cells. J Hepatol. 2000;32(5):754–761. doi:10.1016/S0168-8278(00)80244-5
  • Pi L, Sun C, Jn-Simon N, et al. CCN2/CTGF promotes liver fibrosis through crosstalk with the Slit2/Robo signaling. J Cell Commun Signal. 2023;17(1):137–150. doi:10.1007/s12079-022-00713-y
  • George J, Tsutsumi M. siRNA-mediated knockdown of connective tissue growth factor prevents N-nitrosodimethylamine-induced hepatic fibrosis in rats. Gene Ther. 2007;14(10):790–803. doi:10.1038/sj.gt.3302929
  • Li S, Lv YF, Su HQ, Zhang QN, Wang LR, Hao ZM. A virus-like particle-based connective tissue growth factor vaccine suppresses carbon tetrachloride-induced hepatic fibrosis in mice. Sci Rep. 2016;6:32155. doi:10.1038/srep32155
  • Ren J, Wang X, Parry SN, et al. Targeting CCN2 protects against progressive non-alcoholic steatohepatitis in a preclinical model induced by high-fat feeding and type 2 diabetes. J Cell Commun Signal. 2022;16(3):447–460. doi:10.1007/s12079-022-00667-1
  • Sgalla G, Franciosa C, Simonetti J, Richeldi L. Pamrevlumab for the treatment of idiopathic pulmonary fibrosis. Expert Opin Investig Drugs. 2020;29(8):771–777. doi:10.1080/13543784.2020.1773790
  • Fu M, Peng D, Lan T, Wei Y, Wei X. Multifunctional regulatory protein connective tissue growth factor (CTGF): a potential therapeutic target for diverse diseases. Acta Pharm Sin B. 2022;12(4):1740–1760. doi:10.1016/j.apsb.2022.01.007
  • Sun S, Ding Z, Yang X, et al. Nanobody: a small antibody with big implications for tumor therapeutic strategy. Int J Nanomedicine. 2021;16:2337–2356. doi:10.2147/IJN.S297631
  • Ma L, Zhu M, Li G, et al. Preclinical development of a long-acting trivalent bispecific nanobody targeting IL-5 for the treatment of eosinophilic asthma. Respir Res. 2022;23(1):316. doi:10.1186/s12931-022-02240-1
  • Jovcevska I, Muyldermans S. The therapeutic potential of nanobodies. BioDrugs. 2020;34(1):11–26. doi:10.1007/s40259-019-00392-z
  • Wang W, Xu C, Wang H, Jiang C. Identification of nanobodies against hepatocellular carcinoma marker glypican-3. Mol Immunol. 2021;131:13–22. doi:10.1016/j.molimm.2021.01.010
  • Ma L, Zhu M, Gai J, et al. Preclinical development of a novel CD47 nanobody with less toxicity and enhanced anti-cancer therapeutic potential. J Nanobiotechnology. 2020;18(1):12. doi:10.1186/s12951-020-0571-2
  • van der Linden RH, Frenken LG, de Geus B, et al. Comparison of physical chemical properties of llama VHH antibody fragments and mouse monoclonal antibodies. Biochim Biophys Acta. 1999;1431(1):37–46. doi:10.1016/S0167-4838(99)00030-8
  • Papp KA, Weinberg MA, Morris A, Reich K. IL17A/F nanobody sonelokimab in patients with plaque psoriasis: a multicentre, randomised, placebo-controlled, phase 2b study. Lancet. 2021;397(10284):1564–1575. doi:10.1016/S0140-6736(21)00440-2
  • Van Roy M, Ververken C, Beirnaert E, et al. The preclinical pharmacology of the high affinity anti-IL-6R nanobody(R) ALX-0061 supports its clinical development in rheumatoid arthritis. Arthritis Res Ther. 2015;17(1):135. doi:10.1186/s13075-015-0651-0
  • Li S, Li X, Chen F, Liu M, Ning L, Yan Y. Nobiletin mitigates hepatocytes death, liver inflammation, and fibrosis in a murine model of NASH through modulating hepatic oxidative stress and mitochondrial dysfunction. J Nutr Biochem. 2022;100:108888. doi:10.1016/j.jnutbio.2021.108888
  • Navarro-Corcuera A, Lopez-Zabalza MJ, Martinez-Irujo JJ, et al. Role of AGAP2 in the profibrogenic effects induced by TGFbeta in LX-2 hepatic stellate cells. Biochim Biophys Acta Mol Cell Res. 2019;1866(4):673–685. doi:10.1016/j.bbamcr.2019.01.008
  • Friedman SL, Pinzani M. Hepatic fibrosis 2022: unmet needs and a blueprint for the future. Hepatology. 2022;75(2):473–488. doi:10.1002/hep.32285
  • Brenner MC, Krzyzanski W, Chou JZ, et al. FG-3019, a human monoclonal antibody recognizing connective tissue growth factor, is subject to target-mediated drug disposition. Pharm Res. 2016;33(8):1833–1849. doi:10.1007/s11095-016-1918-0
  • Kaasboll OJ, Gadicherla AK, Wang JH, et al. Connective tissue growth factor (CCN2) is a matricellular preproprotein controlled by proteolytic activation. J Biol Chem. 2018;293(46):17953–17970. doi:10.1074/jbc.RA118.004559
  • Richeldi L, Fernandez Perez ER, Costabel U, et al. Pamrevlumab, an anti-connective tissue growth factor therapy, for idiopathic pulmonary fibrosis (PRAISE): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2020;8(1):25–33. doi:10.1016/S2213-2600(19)30262-0
  • Xue X, Fan X, Qu Q, Wu G. Bioscreening and expression of a camel anti-CTGF VHH nanobody and its renaturation by a novel dialysis-dilution method. AMB Express. 2016;6(1):72. doi:10.1186/s13568-016-0249-1
  • Xu L, Hui AY, Albanis E, et al. Human hepatic stellate cell lines, LX-1 and LX-2: new tools for analysis of hepatic fibrosis. Gut. 2005;54(1):142–151. doi:10.1136/gut.2004.042127
  • Lu ZN, Niu WX, Zhang N, et al. Pantoprazole ameliorates liver fibrosis and suppresses hepatic stellate cell activation in bile duct ligation rats by promoting YAP degradation. Acta Pharmacol Sin. 2021;42(11):1808–1820. doi:10.1038/s41401-021-00754-w
  • Adler SG, Schwartz S, Williams ME, et al. Phase 1 study of anti-CTGF monoclonal antibody in patients with diabetes and microalbuminuria. Clin J Am Soc Nephrol. 2010;5(8):1420–1428. doi:10.2215/CJN.09321209
  • Li G, Xie Q, Shi Y, et al. Inhibition of connective tissue growth factor by siRNA prevents liver fibrosis in rats. J Gene Med. 2006;8(7):889–900. doi:10.1002/jgm.894
  • Paradis V, Perlemuter G, Bonvoust F, et al. High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. Hepatology. 2001;34(4 Pt 1):738–744. doi:10.1053/jhep.2001.28055
  • Gressner OA, Gressner AM. Connective tissue growth factor: a fibrogenic master switch in fibrotic liver diseases. Liver Int. 2008;28(8):1065–1079. doi:10.1111/j.1478-3231.2008.01826.x