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Targeting Bone Marrow-Derived Fibroblasts for Renal Fibrosis

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Renal Fibrosis: Mechanisms and Therapies

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1165))

Abstract

Renal fibrosis is a major pathological feature of chronic kidney disease, which is characterized by massive fibroblast activation and excessive production and deposition of extracellular matrix (ECM). Renal fibrosis results in progressive loss of kidney function; however, there is currently no effective therapy available clinically to treat or even reverse renal fibrosis. Although activated fibroblasts/myofibroblasts are responsible for the production and deposition of ECM, their origin has been debatable. Recent studies have provided compelling evidence that bone marrow-derived fibroblast precursors contribute significantly to the population of myofibroblasts and the development of renal fibrosis. Therefore, targeting the molecular signaling mechanisms underlying the recruitment and activation of the bone marrow-derived fibroblast precursors may serve as novel therapeutic strategy for chronic kidney disease. In this review, we appraise recent advances in our understanding of the recruitment and activation of bone marrow-derived fibroblast precursors in the kidney and the development of renal fibrosis and highlight novel molecular signaling pathways that may lead to the development of new therapies for chronic kidney disease.

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References

  • Abe R, Donnelly SC, Peng T, Bucala R, Metz CN (2001) Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J Immunol 166:7556–7562

    Article  CAS  PubMed  Google Scholar 

  • Abel S, Hundhausen C, Mentlein R, Schulte A, Berkhout TA, Broadway N et al (2004) The transmembrane CXC-chemokine ligand 16 is induced by IFN-gamma and TNF-alpha and shed by the activity of the disintegrin-like metalloproteinase ADAM10. J Immunol 172:6362–6372

    Article  CAS  PubMed  Google Scholar 

  • Alkhatib G, Liao F, Berger EA, Farber JM, Peden KW (1997) A new SIV co-receptor, STRL33. Nature 388:238

    Article  CAS  PubMed  Google Scholar 

  • Bielesz B, Sirin Y, Si H, Niranjan T, Gruenwald A, Ahn S et al (2010) Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans. J Clin Invest 120:4040–4054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Border WA, Noble NA (1994) Transforming growth factor beta in tissue fibrosis. N Engl J Med 331:1286–1292

    Article  CAS  PubMed  Google Scholar 

  • Border WA, Okuda S, Languino LR, Sporn MB, Ruoslahti E (1990) Suppression of experimental glomerulonephritis by antiserum against transforming growth factor beta 1. Nature 346:371–374

    Article  CAS  PubMed  Google Scholar 

  • Bottinger EP, Bitzer M (2002) TGF-beta signaling in renal disease. J Am Soc Nephrol 13:2600–2610

    Article  PubMed  Google Scholar 

  • Broekema M, Harmsen MC, van Luyn MJ, Koerts JA, Petersen AH, van Kooten TG et al (2007) Bone marrow-derived myofibroblasts contribute to the renal interstitial myofibroblast population and produce procollagen I after ischemia/reperfusion in rats. J Am Soc Nephrol 18:165–175

    Article  CAS  PubMed  Google Scholar 

  • Bucala R, Spiegel LA, Chesney J, Hogan M, Cerami A (1994) Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med 1:71–81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buchtler S, Grill A, Hofmarksrichter S, Stöckert P, Schiechl-Brachner G, Rodriguez Gomez M et al (2018) Cellular origin and functional relevance of collagen I production in the kidney. J Am Soc Nephrol 29:1859–1873

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen G, Lin SC, Chen J, He L, Dong F, Xu J et al (2011) CXCL16 recruits bone marrow-derived fibroblast precursors in renal fibrosis. J Am Soc Nephrol 22:1876–1886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen J, Xia Y, Lin X, Feng XH, Wang Y (2014) Smad3 signaling activates bone marrow-derived fibroblasts in renal fibrosis. Lab Invest 94:545–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chesney J, Bacher M, Bender A, Bucala R (1997) The peripheral blood fibrocyte is a potent antigen-presenting cell capable of priming naive T cells in situ. Proc Natl Acad Sci U S A 94:6307–6312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conway B, Hughes J (2012) Cellular orchestrators of renal fibrosis. QJM: Mon J Assoc Physicians 105:611–615

    Article  CAS  Google Scholar 

  • Corton JM, Gillespie JG, Hawley SA, Hardie DG (1995) 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur J Biochem 229:558–565

    Article  CAS  PubMed  Google Scholar 

  • Deng HK, Unutmaz D, KewalRamani VN, Littman DR (1997) Expression cloning of new receptors used by simian and human immunodeficiency viruses. Nature 388:296–300

    Article  CAS  PubMed  Google Scholar 

  • Dong Y, Yang M, Zhang J, Peng X, Cheng J, Cui T et al (2016) Depletion of CD8+ T cells exacerbates CD4+ T cell-induced monocyte-to-fibroblast transition in renal fibrosis. J Immunol 196:1874–1881

    Article  CAS  PubMed  Google Scholar 

  • Duerrschmid C, Trial J, Wang Y, Entman ML, Haudek SB (2015) Tumor necrosis factor: a mechanistic link between angiotensin-II-induced cardiac inflammation and fibrosis. Circ Heart Fail 8:352–361

    Article  CAS  PubMed  Google Scholar 

  • Ebert LM, Schaerli P, Moser B (2005) Chemokine-mediated control of T cell traffic in lymphoid and peripheral tissues. Mol Immunol 42:799–809

    Article  CAS  PubMed  Google Scholar 

  • Eddy AA (2005) Progression in chronic kidney disease. Adv Chronic Kidney Dis 12:353–365

    Article  PubMed  Google Scholar 

  • Eddy AA (2013) The origin of scar-forming kidney myofibroblasts. Nat Med 19:964–966

    Article  CAS  PubMed  Google Scholar 

  • Elewa U, Sanchez-Nino MD, Mahillo-Fernandez I, Martin-Cleary C, Belen Sanz A, Perez-Gomez MV et al (2016) Circulating CXCL16 in diabetic kidney disease. Kidney Blood Press Res 41:663–671

    Article  CAS  PubMed  Google Scholar 

  • Essawy M, Soylemezoglu O, Muchaneta-Kubara EC, Shortland J, Brown CB, el Nahas AM (1997) Myofibroblasts and the progression of diabetic nephropathy. Nephrol Dial Transpl Off Publ Eur Dial Transpl Assoc Eur Ren Assoc 12:43–50

    CAS  Google Scholar 

  • Farris AB, Colvin RB (2012) Renal interstitial fibrosis: mechanisms and evaluation. Curr Opin Nephrol Hypertens 21:289–300

    Article  PubMed  PubMed Central  Google Scholar 

  • Forster R, Davalos-Misslitz AC, Rot A (2008) CCR25 and its ligands: balancing immunity and tolerance. Nat Rev Immunol 8:362–371

    Article  PubMed  CAS  Google Scholar 

  • Gordon S, Martinez FO (2010) Alternative activation of macrophages: mechanism and functions. Immunity 32:593–604

    Article  CAS  PubMed  Google Scholar 

  • Gough PJ, Garton KJ, Wille PT, Rychlewski M, Dempsey PJ, Raines EW (2004) A disintegrin and metalloproteinase 10-mediated cleavage and shedding regulates the cell surface expression of CXC chemokine ligand 16. J Immunol 172:3678–3685

    Article  CAS  PubMed  Google Scholar 

  • Grimm PC, Nickerson P, Jeffery J, Savani RC, Gough J, McKenna RM et al (2001) Neointimal and tubulointerstitial infiltration by recipient mesenchymal cells in chronic renal-allograft rejection. N Engl J Med 345:93–97

    Article  CAS  PubMed  Google Scholar 

  • Haudek SB, Cheng J, Du J, Wang Y, Hermosillo-Rodriguez J, Trial J et al (2010) Monocytic fibroblast precursors mediate fibrosis in angiotensin-II-induced cardiac hypertrophy. J Mol Cell Cardiol 49:499–507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herzog EL, Bucala R (2010) Fibrocytes in health and disease. Exp Hematol 38:548–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang XR, Chung AC, Yang F, Yue W, Deng C, Lau CP et al (2010) Smad3 mediates cardiac inflammation and fibrosis in angiotensin II-induced hypertensive cardiac remodeling. Hypertension 55:1165–1171

    Article  CAS  PubMed  Google Scholar 

  • Humphreys BD, Lin SL, Kobayashi A, Hudson TE, Nowlin BT, Bonventre JV et al (2010) Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. Am J Pathol 176:85–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iwano M, Plieth D, Danoff TM, Xue C, Okada H, Neilson EG (2002) Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest 110:341–350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iwashima Y, Horio T, Kumada M, Suzuki Y, Kihara S, Rakugi H et al (2006) Adiponectin and renal function, and implication as a risk of cardiovascular disease. Am J Cardiol 98:1603–1608

    Article  CAS  PubMed  Google Scholar 

  • Izquierdo MC, Sanz AB, Mezzano S, Blanco J, Carrasco S, Sanchez-Niño MD et al (2012) TWEAK (tumor necrosis factor-like weak inducer of apoptosis) activates CXCL16 expression during renal tubulointerstitial inflammation. Kidney Int 81:1098–1107

    Article  CAS  PubMed  Google Scholar 

  • Izquierdo MC, Martin-Cleary C, Fernandez-Fernandez B, Elewa U, Sanchez-Niño MD, Carrero JJ et al (2014) CXCL16 in kidney and cardiovascular injury. Cytokine Growth Factor Rev 25:317–325

    Article  CAS  PubMed  Google Scholar 

  • Lan HY (2011) Diverse roles of TGF-beta/Smads in renal fibrosis and inflammation. Int J Biol Sci 7:1056–1067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Latella G, Vetuschi A, Sferra R, Catitti V, D’Angelo A, Zanninelli G et al (2009) Targeted disruption of Smad3 confers resistance to the development of dimethylnitrosamine-induced hepatic fibrosis in mice. Liver Int 29:997–1009

    Article  CAS  PubMed  Google Scholar 

  • Lebleu VS, Taduri G, O’Connell J, Teng Y, Cooke VG, Woda C et al (2013) Origin and function of myofibroblasts in kidney fibrosis. Nat Med 19:1047–1053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee S, Huen S, Nishio H, Nishio S, Lee HK, Choi BS et al (2011) Distinct macrophage phenotypes contribute to kidney injury and repair. J Am Soc Nephrol 22:317–326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li J, Deane JA, Campanale NV, Bertram JF, Ricardo SD et al (2007) The contribution of bone marrow-derived cells to the development of renal interstitial fibrosis. Stem Cells 25:697–706

    Article  CAS  PubMed  Google Scholar 

  • Liang H, Ma Z, Peng H, He L, Hu Z, Wang Y (2016) CXCL16 deficiency attenuates renal injury and fibrosis in salt-sensitive hypertension. Sci Rep 6:28715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang H, Zhang Z, Yan J, Wang Y, Hu Z, Mitch WE et al (2017) The IL-4 receptor alpha has a critical role in bone marrow-derived fibroblast activation and renal fibrosis. Kidney Int 92:1433–1443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin SL, Kisseleva T, Brenner DA, Duffield JS (2008) Pericytes and perivascular fibroblasts are the primary source of collagen-producing cells in obstructive fibrosis of the kidney. Am J Pathol 173:1617–1627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin Z, Gong Q, Zhou Z, Zhang W, Liao S, Liu Y et al (2011) Increased plasma CXCL16 levels in patients with chronic kidney diseases. Eur J Clin Invest 41:836–845

    Article  CAS  PubMed  Google Scholar 

  • Liu Y (2010) New insights into epithelial-mesenchymal transition in kidney fibrosis. J Am Soc Nephrol 21:212–222

    Article  CAS  PubMed  Google Scholar 

  • Loetscher M, Amara A, Oberlin E, Brass N, Legler D, Loetscher P et al (1997) TYMSTR, a putative chemokine receptor selectively expressed in activated T cells, exhibits HIV-1 coreceptor function. Curr Biol 7:652–660

    Article  CAS  PubMed  Google Scholar 

  • Ludwig A, Weber C (2007) Transmembrane chemokines: versatile ‘special agents’ in vascular inflammation. Thromb Haemost 97:694–703

    Article  CAS  PubMed  Google Scholar 

  • Ludwig A, Hundhausen C, Lambert MH, Broadway N, Andrews RC, Bickett DM et al (2005) Metalloproteinase inhibitors for the disintegrin-like metalloproteinases ADAM10 and ADAM17 that differentially block constitutive and phorbol ester-inducible shedding of cell surface molecules. Comb Chem High Throughput Screen 8:161–171

    Article  CAS  PubMed  Google Scholar 

  • Ma Z, Jin X, He L, Wang Y (2016) CXCL16 regulates renal injury and fibrosis in experimental renal artery stenosis. Am J Physiol Heart Circ Physiol 311:H815–H821

    Article  PubMed  PubMed Central  Google Scholar 

  • Mackay CR (2001) Chemokines: immunology’s high impact factors. Nat Immunol 2:95–101

    Article  CAS  PubMed  Google Scholar 

  • Matloubian M, David A, Engel S, Ryan JE, Cyster JG (2000) A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nat Immunol 1:298–304

    Article  CAS  PubMed  Google Scholar 

  • Meng XM, Tang PM, Li J, Lan HY (2015) TGF-beta/Smad signaling in renal fibrosis. Front Physiol 6:82

    Article  PubMed  PubMed Central  Google Scholar 

  • Meran S, Steadman R (2011) Fibroblasts and myofibroblasts in renal fibrosis. Int J Exp Pathol 92:158–167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mills KT, Hamm LL, Alper AB, Miller C, Hudaihed A, Balamuthusamy S et al (2013) Circulating adipocytokines and chronic kidney disease. PLoS ONE 8:e76902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moeller A, Gilpin SE, Ask K, Cox G, Cook D, Gauldie J et al (2009) Circulating fibrocytes are an indicator of poor prognosis in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 179:588–594

    Article  PubMed  Google Scholar 

  • Moore BB, Kolodsick JE, Thannickal VJ, Cooke K, Moore TA, Hogaboam C et al (2005) CCR57-mediated recruitment of fibrocytes to the alveolar space after fibrotic injury. Am J Pathol 166:675–684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mori L, Bellini A, Stacey MA, Schmidt M, Mattoli S (2005) Fibrocytes contribute to the myofibroblast population in wounded skin and originate from the bone marrow. Exp Cell Res 304:81–90

    Article  CAS  PubMed  Google Scholar 

  • Nath KA (1992) Tubulointerstitial changes as a major determinant in the progression of renal damage. Am J Kidney Dis 20:1–17

    Article  CAS  PubMed  Google Scholar 

  • Neilson EG (2006) Mechanisms of disease: Fibroblasts–a new look at an old problem. Nat Clin Pract Nephrol 2:101–108

    Article  CAS  PubMed  Google Scholar 

  • Niedermeier M, Reich B, Rodriguez Gomez M, Denzel A, Schmidbauer K, Göbel N et al (2009) CD4+ T cells control the differentiation of Gr1+ monocytes into fibrocytes. Proc Natl Acad Sci U S A 106:17892–17897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okamura DM, Lopez-Guisa JM, Koelsch K, Collins S, Eddy AA (2007) Atherogenic scavenger receptor modulation in the tubulointerstitium in response to chronic renal injury. Am J Physiol Renal Physiol 293:F575–F585

    Article  CAS  PubMed  Google Scholar 

  • Phillips RJ, Burdick MD, Hong K, Lutz MA, Murray LA, Xue YY et al (2004) Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. J Clin Invest 114:438–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Powell DW, Mifflin RC, Valentich JD, Crowe SE, Saada JI, West AB (1999) Myofibroblasts. I. Paracrine cells important in health and disease. Am J Physiol 277:C1–C9

    Article  CAS  PubMed  Google Scholar 

  • Reich B, Schmidbauer K, Rodriguez Gomez M, Johannes Hermann F, Göbel N, Brühl H et al (2013) Fibrocytes develop outside the kidney but contribute to renal fibrosis in a mouse model. Kidney Int 84:78–89

    Article  CAS  PubMed  Google Scholar 

  • Roberts IS, Burrows C, Shanks JH, Venning M, McWilliam LJ (1997) Interstitial myofibroblasts: predictors of progression in membranous nephropathy. J Clin Pathol 50:123–127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rollins BJ (1997) Chemokines. Blood 90:909–928

    CAS  PubMed  Google Scholar 

  • Roufosse C, Bou-Gharios G, Prodromidi E, Alexakis C, Jeffery R, Khan S et al (2006) Bone marrow-derived cells do not contribute significantly to collagen I synthesis in a murine model of renal fibrosis. J Am Soc Nephrol 17:775–782

    Article  CAS  PubMed  Google Scholar 

  • Sakai N, Wada T, Yokoyama H, Lipp M, Ueha S, Matsushima K et al (2006) Secondary lymphoid tissue chemokine (SLC/CCL21)/CCR69 signaling regulates fibrocytes in renal fibrosis. Proc Natl Acad Sci U S A 103:14098–14103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sato M, Muragaki Y, Saika S, Roberts AB, Ooshima A (2003) Targeted disruption of TGF-beta1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. J Clin Invest 112:1486–1494

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulte A, Schulz B, Andrzejewski MG, Hundhausen C, Mletzko S, Achilles J et al (2007) Sequential processing of the transmembrane chemokines CX3CL1 and CXCL16 by alpha- and gamma-secretases. Biochem Biophys Res Commun 358:233–240

    Article  CAS  PubMed  Google Scholar 

  • Shachar I (2017) An essential MIF-CD74 signaling axis in kidney tubular regeneration, with prospects for precision medicine and pharmacological augmentation. Am J Physiol Renal Physiol 313:F1084–F1086

    Article  PubMed  CAS  Google Scholar 

  • Shao DD, Suresh R, Vakil V, Gomer RH, Pilling D (2008) Pivotal Advance: Th-1 cytokines inhibit, and Th-2 cytokines promote fibrocyte differentiation. J Leukoc Biol 83:1323–1333

    Article  CAS  PubMed  Google Scholar 

  • Shimaoka T, Kume N, Minami M, Hayashida K, Kataoka H, Kita T et al (2000) Molecular cloning of a novel scavenger receptor for oxidized low density lipoprotein, SR-PSOX, on macrophages. J Biol Chem 275:40663–40666

    Article  CAS  PubMed  Google Scholar 

  • Shimaoka T, Nakayama T, Fukumoto N, Kume N, Takahashi S, Yamaguchi J et al (2004) Cell surface-anchored SR-PSOX/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6-expressing cells. J Leukoc Biol 75:267–274

    Article  CAS  PubMed  Google Scholar 

  • Shimotomai T, Kakei M, Narita T, Koshimura J, Hosoba M, Kato M et al (2005) Enhanced urinary adiponectin excretion in IgA-nephropathy patients with proteinuria. Ren Fail 27:323–328

    Article  CAS  PubMed  Google Scholar 

  • Strutz F, Zeisberg M (2006) Renal fibroblasts and myofibroblasts in chronic kidney disease. J Am Soc Nephrol 17:2992–2998

    Article  CAS  PubMed  Google Scholar 

  • Tapmeier TT, Fearn A, Brown K, Chowdhury P, Sacks SH, Sheerin NS et al (2010) Pivotal role of CD4+ T cells in renal fibrosis following ureteric obstruction. Kidney Int 78:351–362

    Article  CAS  PubMed  Google Scholar 

  • Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA (2002) Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol 3:349–363

    Article  CAS  PubMed  Google Scholar 

  • Verrecchia F, Chu ML, Mauviel A (2001) Identification of novel TGF-beta/Smad gene targets in dermal fibroblasts using a combined cDNA microarray/promoter transactivation approach. J Biol Chem 276:17058–17062

    Article  CAS  PubMed  Google Scholar 

  • Wang S, Meng XM, Ng YY, Ma FY, Zhou S, Zhang Y et al (2016) TGF-β/Smad3 signalling regulates the transition of bone marrow-derived macrophages into myofibroblasts during tissue fibrosis. Oncotarget 7:8809–8822

    PubMed  Google Scholar 

  • Wang Y, Jia L, Hu Z, Entman ML, Mitch WE, Wang Y (2018) AMP-activated protein kinase/myocardin-related transcription factor-A signaling regulates fibroblast activation and renal fibrosis. Kidney Int 93:81–94

    Article  CAS  PubMed  Google Scholar 

  • Wilbanks A, Zondlo SC, Murphy K, Mak S, Soler D, Langdon P et al (2001) Expression cloning of the STRL33/BONZO/TYMSTRligand reveals elements of CC, CXC, and CX3C chemokines. J Immunol 166:5145–5154

    Article  CAS  PubMed  Google Scholar 

  • Wynn TA (2004) Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol 4:583–594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wynn TA, Barron L (2010) Macrophages: master regulators of inflammation and fibrosis. Semin Liver Dis 30:245–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xia Y, Entman ML, Wang Y (2013a) CCR2 regulates the uptake of bone marrow-derived fibroblasts in renal fibrosis. PLoS ONE 8:e77493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xia Y, Entman ML, Wang Y (2013b) Critical role of CXCL16 in hypertensive kidney injury and fibrosis. Hypertension 62:1129–1137

    Article  CAS  PubMed  Google Scholar 

  • Xia Y, Jin X, Yan J, Entman ML, Wang Y (2014a) CXCR88 plays a critical role in angiotensin II-induced renal injury and fibrosis. Arterioscler Thromb Vasc Biol 34:1422–1428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xia Y, Yan J, Jin X, Entman ML, Wang Y (2014b) The chemokine receptor CXCR89 contributes to recruitment of bone marrow-derived fibroblast precursors in renal fibrosis. Kidney Int 86:327–337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu J, Lin SC, Chen J, Miao Y, Taffet GE, Entman ML et al (2011) CCR90 mediates the uptake of bone marrow-derived fibroblast precursors in angiotensin II-induced cardiac fibrosis. Am J Physiol Heart Circ Physiol 301:H538–H547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan J, Zhang Z, Yang J, Mitch WE, Wang Y (2015) JAK3/STAT6 stimulates bone marrow-derived fibroblast activation in renal fibrosis. J Am Soc Nephrol 26:3060–3071

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan J, Zhang Z, Jia L, Wang Y (2016) Role of bone marrow-derived fibroblasts in renal fibrosis. Front Physiol 7:61

    PubMed  PubMed Central  Google Scholar 

  • Yang J, Lin SC, Chen G, He L, Hu Z, Chan L et al (2013) Adiponectin promotes monocyte-to-fibroblast transition in renal fibrosis. J Am Soc Nephrol 24:1644–1659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeisberg M, Kalluri R (2004) The role of epithelial-to-mesenchymal transition in renal fibrosis. J Mol Med 82:175–181

    Article  PubMed  Google Scholar 

  • Zeisberg M, Kalluri R (2015) Physiology of the renal interstitium. Clin J Am Soc Nephrol 10:1831–1840

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeisberg M, Neilson EG (2010) Mechanisms of tubulointerstitial fibrosis. J Am Soc Nephrol 21:1819–1834

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang G, Moorhead PJ, el Nahas AM (1995) Myofibroblasts and the progression of experimental glomerulonephritis. Exp Nephrol 3:308–318

    CAS  PubMed  Google Scholar 

  • Zhao J, Shi W, Wang YL, Chen H, Bringas P Jr, Datto MB et al (2002) Smad3 deficiency attenuates bleomycin-induced pulmonary fibrosis in mice. Am J Physiol Lung Cell Mol Physiol 282:L585–L593

    Article  CAS  PubMed  Google Scholar 

  • Zhao L, Wu F, Jin L, Lu T, Yang L, Pan X et al (2014) Serum CXCL16 as a novel marker of renal injury in type 2 diabetes mellitus. PLoS ONE 9:e87786

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zlotnik A, Yoshie O (2012) The chemokine superfamily revisited. Immunity 36:705–716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zoccali C, Mallamaci F (2011) Adiponectin and leptin in chronic kidney disease: causal factors or mere risk markers? J Ren Nutr 21:87–91

    Article  CAS  PubMed  Google Scholar 

  • Zoccali C, Mallamaci F, Panuccio V, Tripepi G, Cutrupi S, Parlongo S et al (2003) Adiponectin is markedly increased in patients with nephrotic syndrome and is related to metabolic risk factors. Kidney Int Suppl 84:S98–S102

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by grants from the National Institutes of Health grant (R01DK95835) and the US Department of Veterans Administration grant (I01BX02650) to YW. This chapter was modified from an article authored by our group in Frontiers in Physiology (Yan et al. 2016). The related contents are reused with permission.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be considered as a potential conflict of interest.

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An, C., Jia, L., Wen, J., Wang, Y. (2019). Targeting Bone Marrow-Derived Fibroblasts for Renal Fibrosis. In: Liu, BC., Lan, HY., Lv, LL. (eds) Renal Fibrosis: Mechanisms and Therapies. Advances in Experimental Medicine and Biology, vol 1165. Springer, Singapore. https://doi.org/10.1007/978-981-13-8871-2_14

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