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Hepatic macrophages act as a central hub for relaxin-mediated alleviation of liver fibrosis

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  • 1.

    Troeger, J. S. et al. Deactivation of hepatic stellate cells during liver fibrosis resolution in mice. Gastroenterology 143, 1073–1083. e1022 (2012).

    CAS  Google Scholar 

  • 2.

    Hu, M. et al. Relaxin gene delivery mitigates liver metastasis and synergizes with check point therapy. Nat. Commun. 10, 2993 (2019).

    Google Scholar 

  • 3.

    Fallowfield, J. A. et al. Relaxin modulates human and rat hepatic myofibroblast function and ameliorates portal hypertension in vivo. Hepatology 59, 1492–1504 (2014).

    CAS  Google Scholar 

  • 4.

    Tacke, F. & Zimmermann, H. W. Macrophage heterogeneity in liver injury and fibrosis. J. Hepatol. 60, 1090–1096 (2014).

    CAS  Google Scholar 

  • 5.

    Ramachandran, P. et al. Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis. Proc. Natl Acad. Sci. USA 109, E3186–E3195 (2012).

    CAS  Google Scholar 

  • 6.

    Pellicoro, A., Ramachandran, P., Iredale, J. P. & Fallowfield, J. A. Liver fibrosis and repair: immune regulation of wound healing in a solid organ. Nat. Rev. Immunol. 14, 181–194 (2014).

    CAS  Google Scholar 

  • 7.

    Francis, H. et al. Regulation of the extrinsic apoptotic pathway by microRNA-21 in alcoholic liver injury. J. Biol. Chem. 289, 27526–27539 (2014).

    CAS  Google Scholar 

  • 8.

    Chen, S. A. et al. The pharmacokinetics of recombinant human relaxin in nonpregnant women after intravenous, intravaginal, and intracervical administration. Pharma. Res 10, 834–838 (1993).

    CAS  Google Scholar 

  • 9.

    Uhlén, M. et al. Tissue-based map of the human proteome. Science 347, 1260419 (2015).

    Google Scholar 

  • 10.

    Friedman, S. L. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol. Rev. 88, 125–172 (2008).

    CAS  Google Scholar 

  • 11.

    Hu, M. & Huang, L. Nanomaterial manipulation of immune microenvironment in the diseased liver. Adv. Funct. Mater. 29, 1805760 (2019).

    Google Scholar 

  • 12.

    Kushiyama, T. et al. Alteration in the phenotype of macrophages in the repair of renal interstitial fibrosis in mice. Nephrology 16, 522–535 (2011).

    CAS  Google Scholar 

  • 13.

    Ma, P. F. et al. Cytotherapy with M1-polarized macrophages ameliorates liver fibrosis by modulating immune microenvironment in mice. J. Hepatol. 67, 770–779 (2017).

    CAS  Google Scholar 

  • 14.

    Kern, K. et al. CD200 selectively upregulates prostaglandin E2 and D2 synthesis in LPS-treated bone marrow-derived macrophages. Prostag. Oth. Lipid Mediat. 133, 53–59 (2017).

    CAS  Google Scholar 

  • 15.

    Wang, M. et al. Chronic alcohol ingestion modulates hepatic macrophage populations and functions in mice. J. Leukoc. Biol. 96, 657–665 (2014).

    Google Scholar 

  • 16.

    Liaskou, E. et al. Monocyte subsets in human liver disease show distinct phenotypic and functional characteristics. Hepatology 57, 385–398 (2013).

    CAS  Google Scholar 

  • 17.

    Zimmermann, H. W. et al. Functional contribution of elevated circulating and hepatic non-classical CD14 + CD16 + monocytes to inflammation and human liver fibrosis. PloS ONE 5, e11049 (2010).

    Google Scholar 

  • 18.

    Krenkel, O. & Tacke, F. Liver macrophages in tissue homeostasis and disease. Nat. Rev. Immunol. 17, 306–321 (2017).

    CAS  Google Scholar 

  • 19.

    Hanna, R. N. et al. The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C monocytes. Nat. Immunol. 12, 778–785 (2011).

    CAS  Google Scholar 

  • 20.

    Mildner, A. et al. Genomic characterization of murine monocytes reveals C/EBPβ transcription factor dependence of Ly6C cells. Immunity 46, 849–862. e847 (2017).

    CAS  Google Scholar 

  • 21.

    Palumbo-Zerr, K. et al. Orphan nuclear receptor NR4A1 regulates transforming growth factor-β signaling and fibrosis. Nat. Med. 21, 150–158 (2015).

    CAS  Google Scholar 

  • 22.

    Hsu, S. Y. et al. Activation of orphan receptors by the hormone relaxin. Science 295, 671–674 (2002).

    CAS  Google Scholar 

  • 23.

    Maruoka, H. et al. Dibutyryl-cAMP up-regulates Nur77 expression via histone modification during neurite outgrowth in PC12 cells. J. Biochem. 148, 93–101 (2010).

    CAS  Google Scholar 

  • 24.

    Lough, J., Rosenthall, L., Arzoumanian, A. & Goresky, C. A. Kupffer cell depletion associated with capillarization of liver sinusoids in carbon tetrachloride-induced rat liver cirrhosis. J. Hepatol. 5, 190–198 (1987).

    CAS  Google Scholar 

  • 25.

    Simons, M. & Raposo, G. Exosomes—vesicular carriers for intercellular communication. Curr. Opin. Cell Biol. 21, 575–581 (2009).

    CAS  Google Scholar 

  • 26.

    Valadi, H. et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 9, 654–659 (2007).

    CAS  Google Scholar 

  • 27.

    Kim, K. M., Abdelmohsen, K., Mustapic, M., Kapogiannis, D. & Gorospe, M. RNA in extracellular vesicles. WIREs RNA 8, e1413 (2017).

    Google Scholar 

  • 28.

    Tokar, T. et al. mirDIP 4.1—integrative database of human microRNA target predictions. Nucleic Acids Res. 46, D360–D370 (2017).

    Google Scholar 

  • 29.

    Zhang, P. et al. The deubiquitinating enzyme TNFAIP3 mediates inactivation of hepatic ASK1 and ameliorates nonalcoholic steatohepatitis. Nat. Med. 24, 84–94 (2018).

    CAS  Google Scholar 

  • 30.

    Liles, J. T. et al. ASK1 contributes to fibrosis and dysfunction in models of kidney disease. J. Clin. Investig. 128, 4485–4500 (2018).

    Google Scholar 

  • 31.

    Singh, S., Simpson, R. L. & Bennett, R. G. Relaxin activates peroxisome proliferator-activated receptor γ (PPARγ) through a pathway involving PPARγ coactivator 1α (PGC1α). J. Biol. Chem. 290, 950–959 (2015).

    CAS  Google Scholar 

  • 32.

    Singh, S. & Bennett, R. G. Relaxin signaling activates peroxisome proliferator-activated receptor gamma. Mol. Cell. Endocrinol. 315, 239–245 (2010).

    CAS  Google Scholar 

  • 33.

    Hazra, S., Miyahara, T., Rippe, R. A. & Tsukamoto, H. PPAR gamma and hepatic stellate cells. Comp. Hepatol. 3, S7 (2004).

    Google Scholar 

  • 34.

    Wei, J. et al. PPARγ downregulation by TGF-β in fibroblast and impaired expression and function in systemic sclerosis: a novel mechanism for progressive fibrogenesis. PloS ONE 5, e13778 (2010).

    Google Scholar 

  • 35.

    Chibon, F. et al. ASK1 (MAP3K5) as a potential therapeutic target in malignant fibrous histiocytomas with 12q14–q15 and 6q23 amplifications. Genes Chromosomes Cancer 40, 32–37 (2004).

    CAS  Google Scholar 

  • 36.

    Tang, X. et al. An RNA interference-based screen identifies MAP4K4/NIK as a negative regulator of PPARγ, adipogenesis, and insulin-responsive hexose transport. Proc. Natl Acad. Sci. USA 103, 2087–2092 (2006).

    CAS  Google Scholar 

  • 37.

    Xiong, J. et al. hnRNPU/TrkB defines a chromatin accessibility checkpoint for liver injury and nonalcoholic steatohepatitis pathogenesis. Hepatology 71, 1228–1246 (2020).

    CAS  Google Scholar 

  • 38.

    Matsumoto, M. et al. An improved mouse model that rapidly develops fibrosis in non‐alcoholic steatohepatitis. Int. J. Exp. Pathol. 94, 93–103 (2013).

    CAS  Google Scholar 

  • 39.

    Bani, D., Bigazzi, M., Masini, E., Bani, G. & Sacchi, T. B. Relaxin depresses platelet aggregation: in vitro studies on isolated human and rabbit platelets. Lab. Invest. 73, 709–716 (1995).

    CAS  Google Scholar 

  • 40.

    Erikson, M. S. & Unemori, E. N. in Relaxin 2000 (eds Tregear G.W., Ivell R., Bathgate R.A. & Wade J.D.) 373–381 (Springer, 2001).

  • 41.

    Amitrano, L., Guardascione, M. A., Brancaccio, V. & Balzano, A. Coagulation disorders in liver disease. Semin. Liver Dis. 22, 83–96 (2002).

    CAS  Google Scholar 

  • 42.

    Rios, R., Sangro, B., Herrero, I., Quiroga, J. & Prieto, J. The role of thrombopoietin in the thrombocytopenia of patients with liver cirrhosis. Am. J. Gastroenterol. 100, 1311 (2005).

    CAS  Google Scholar 

  • 43.

    Berres, M. L. et al. Antagonism of the chemokine Ccl5 ameliorates experimental liver fibrosis in mice. J. Clin. Investig. 120, 4129–4140 (2010).

    CAS  Google Scholar 

  • 44.

    Mitchell, C. et al. Dual role of CCR2 in the constitution and the resolution of liver fibrosis in mice. Am. J. Pathol. 174, 1766–1775 (2009).

    CAS  Google Scholar 

  • 45.

    Lefebvre, E. et al. Antifibrotic effects of the dual CCR2/CCR5 antagonist cenicriviroc in animal models of liver and kidney fibrosis. PloS ONE 11, e0158156 (2016).

    Google Scholar 

  • 46.

    Banerjee, R., Tyagi, P., Li, S. & Huang, L. Anisamide-targeted stealth liposomes: a potent carrier for targeting doxorubicin to human prostate cancer cells. Int. J. Cancer 112, 693–700 (2004).

    CAS  Google Scholar 

  • 47.

    Constandinou, C., Henderson, N. & Iredale, J. P. in Fibrosis Research: Methods and Protocols (eds Varga, J., David A. Brenner, D. A. & Phan, S. H.) 237–250 (Springer, 2005).

  • 48.

    Wang, Y. et al. Nanoparticle-mediated HMGA1 silencing promotes lymphocyte infiltration and boosts checkpoint blockade immunotherapy for cancer. Adv. Funct. Mater. 28, 1802847 (2018).

    Google Scholar 

  • 49.

    Teerlink, J. R. et al. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet 381, 29–39 (2013).

    CAS  Google Scholar 

  • 50.

    Ying, W., Cheruku, P. S., Bazer, F. W., Safe, S. H. & Zhou, B. Investigation of macrophage polarization using bone marrow derived macrophages. J. Vis. Exp. 76, e50323 (2013).

    Google Scholar 

  • Source: https://www.nature.com/articles/s41565-020-00836-6

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