WNT-dependent interaction between inflammatory fibroblasts and FOLR2+ macrophages promotes fibrosis in chronic kidney disease.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
25 Jan 2024
Historique:
received: 06 03 2023
accepted: 08 01 2024
medline: 26 1 2024
pubmed: 26 1 2024
entrez: 25 1 2024
Statut: epublish

Résumé

Chronic kidney disease (CKD) is a public health problem driven by myofibroblast accumulation, leading to interstitial fibrosis. Heterogeneity is a recently recognized characteristic in kidney fibroblasts in CKD, but the role of different populations is still unclear. Here, we characterize a proinflammatory fibroblast population (named CXCL-iFibro), which corresponds to an early state of myofibroblast differentiation in CKD. We demonstrate that CXCL-iFibro co-localize with macrophages in the kidney and participate in their attraction, accumulation, and switch into FOLR2+ macrophages from early CKD stages on. In vitro, macrophages promote the switch of CXCL-iFibro into ECM-secreting myofibroblasts through a WNT/β-catenin-dependent pathway, thereby suggesting a reciprocal crosstalk between these populations of fibroblasts and macrophages. Finally, the detection of CXCL-iFibro at early stages of CKD is predictive of poor patient prognosis, which shows that the CXCL-iFibro population is an early player in CKD progression and demonstrates the clinical relevance of our findings.

Identifiants

pubmed: 38272907
doi: 10.1038/s41467-024-44886-z
pii: 10.1038/s41467-024-44886-z
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

743

Subventions

Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : INCa_11692

Informations de copyright

© 2024. The Author(s).

Références

Collaboration GBDCKD. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 395, 709–733 (2020).
doi: 10.1016/S0140-6736(20)30045-3
Duffield, J. S. Cellular and molecular mechanisms in kidney fibrosis. J. Clin. Invest. 124, 2299–2306 (2014).
pubmed: 24892703 pmcid: 4038570 doi: 10.1172/JCI72267
Humphreys, B. D. et al. Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. Am. J. Pathol. 176, 85–97 (2010).
pubmed: 20008127 pmcid: 2797872 doi: 10.2353/ajpath.2010.090517
Kramann, R., DiRocco, D. P. & Humphreys, B. D. Understanding the origin, activation and regulation of matrix-producing myofibroblasts for treatment of fibrotic disease. J. Pathol. 231, 273–289 (2013).
pubmed: 24006178 doi: 10.1002/path.4253
Kramann, R. & Humphreys, B. D. Kidney pericytes: roles in regeneration and fibrosis. Semin. Nephrol. 34, 374–383 (2014).
pubmed: 25217266 pmcid: 4163198 doi: 10.1016/j.semnephrol.2014.06.004
Kramann, R. et al. Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis. Cell Stem Cell 16, 51–66 (2015).
pubmed: 25465115 doi: 10.1016/j.stem.2014.11.004
Chang-Panesso, M., Kadyrov, F. F., Machado, F. G., Kumar, A. & Humphreys, B. D. Meis1 is specifically upregulated in kidney myofibroblasts during aging and injury but is not required for kidney homeostasis or fibrotic response. Am. J. Physiol. Renal Physiol. 315, F275–f290 (2018).
pubmed: 29592525 pmcid: 6139520 doi: 10.1152/ajprenal.00030.2018
Kuppe, C. et al. Decoding myofibroblast origins in human kidney fibrosis. Nature 589, 281–286 (2021).
pubmed: 33176333 doi: 10.1038/s41586-020-2941-1
Kuppe, C. et al. Spatial multi-omic map of human myocardial infarction. Nature 608, 766–777 (2022).
pubmed: 35948637 pmcid: 9364862 doi: 10.1038/s41586-022-05060-x
Sugimoto, H., Mundel, T. M., Kieran, M. W. & Kalluri, R. Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol. Ther. 5, 1640–1646 (2006).
pubmed: 17106243 doi: 10.4161/cbt.5.12.3354
Su, S. et al. CD10(+)GPR77(+) Cancer-associated fibroblasts promote cancer formation and chemoresistance by sustaining cancer stemness. Cell 172, 841–856 e816 (2018).
pubmed: 29395328 doi: 10.1016/j.cell.2018.01.009
Ishii, G., Ochiai, A. & Neri, S. Phenotypic and functional heterogeneity of cancer-associated fibroblast within the tumor microenvironment. Adv. Drug Deliv. Rev. 99, 186–196 (2016).
pubmed: 26278673 doi: 10.1016/j.addr.2015.07.007
Ohlund, D. et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J. Exp. Med. 214, 579–596 (2017).
pubmed: 28232471 pmcid: 5339682 doi: 10.1084/jem.20162024
Bartoschek, M. et al. Spatially and functionally distinct subclasses of breast cancer-associated fibroblasts revealed by single cell RNA sequencing. Nat. Commun. 9, 5150 (2018).
pubmed: 30514914 pmcid: 6279758 doi: 10.1038/s41467-018-07582-3
Costa, A. et al. Fibroblast heterogeneity and immunosuppressive environment in human breast cancer. Cancer Cell 33, 463–479.e410 (2018).
pubmed: 29455927 doi: 10.1016/j.ccell.2018.01.011
Givel, A. M. et al. miR200-regulated CXCL12beta promotes fibroblast heterogeneity and immunosuppression in ovarian cancers. Nat. Commun. 9, 1056 (2018).
pubmed: 29535360 pmcid: 5849633 doi: 10.1038/s41467-018-03348-z
Elyada, E. et al. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. Cancer Discov. 9, 1102–1123 (2019).
pubmed: 31197017 pmcid: 6727976 doi: 10.1158/2159-8290.CD-19-0094
Bonneau, C. et al. A subset of activated fibroblasts is associated with distant relapse in early luminal breast cancer. Breast Cancer Res. 22, 76 (2020).
pubmed: 32665033 pmcid: 7362513 doi: 10.1186/s13058-020-01311-9
Pelon, F. et al. Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms. Nat. Commun. 11, 404 (2020).
pubmed: 31964880 pmcid: 6972713 doi: 10.1038/s41467-019-14134-w
Wu, S. Z. et al. Stromal cell diversity associated with immune evasion in human triple-negative breast cancer. Embo. J. 39, e104063 (2020).
pubmed: 32790115 pmcid: 7527929 doi: 10.15252/embj.2019104063
Biffi, G. & Tuveson, D. A. Diversity and biology of cancer-associated fibroblasts. Physiol. Rev. 101, 147–176 (2021).
pubmed: 32466724 doi: 10.1152/physrev.00048.2019
Galbo, P. M. Jr, Zang, X. & Zheng, D. Molecular features of cancer-associated fibroblast subtypes and their implication on cancer pathogenesis, prognosis, and immunotherapy resistance. Clin. Cancer Res. 27, 2636–2647 (2021).
pubmed: 33622705 pmcid: 8102353 doi: 10.1158/1078-0432.CCR-20-4226
Hu, H. et al. Three subtypes of lung cancer fibroblasts define distinct therapeutic paradigms. Cancer Cell 39, 1531–1547.e1510 (2021).
pubmed: 34624218 pmcid: 8578451 doi: 10.1016/j.ccell.2021.09.003
Luo, H. et al. Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment. Nat. Commun. 13, 6619 (2022).
pubmed: 36333338 pmcid: 9636408 doi: 10.1038/s41467-022-34395-2
Cremasco, V. et al. FAP delineates heterogeneous and functionally divergent stromal cells in immune-excluded breast tumors. Cancer Immunol Res 6, 1472–1485 (2018).
pubmed: 30266714 pmcid: 6597261 doi: 10.1158/2326-6066.CIR-18-0098
Biffi, G. et al. IL1-Induced JAK/STAT signaling is antagonized by TGFβ to shape CAF heterogeneity in pancreatic ductal adenocarcinoma. Cancer Discov. 9, 282–301 (2019).
pubmed: 30366930 doi: 10.1158/2159-8290.CD-18-0710
Davidson, S. et al. Single-Cell RNA sequencing reveals a dynamic stromal niche that supports tumor growth. Cell Rep. 31, 107628 (2020).
pubmed: 32433953 pmcid: 7242909 doi: 10.1016/j.celrep.2020.107628
Dominguez, C. X. et al. Single-cell RNA sequencing reveals stromal evolution into LRRC15(+) myofibroblasts as a determinant of patient response to cancer immunotherapy. Cancer Discov. 10, 232–253 (2020).
pubmed: 31699795 doi: 10.1158/2159-8290.CD-19-0644
Kieffer, Y. et al. Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer. Cancer Discov. 10, 1330–1351 (2020).
pubmed: 32434947 doi: 10.1158/2159-8290.CD-19-1384
Sebastian, A. et al. Single-cell transcriptomic analysis of tumor-derived fibroblasts and normal tissue-resident fibroblasts reveals fibroblast heterogeneity in breast cancer. Cancers 12, 1307 (2020).
pubmed: 32455670 pmcid: 7281266 doi: 10.3390/cancers12051307
Hutton, C. et al. Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity. Cancer Cell 39, 1227–1244.e1220 (2021).
pubmed: 34297917 pmcid: 8443274 doi: 10.1016/j.ccell.2021.06.017
Obradovic, A. et al. Immunostimulatory cancer-associated fibroblast subpopulations can predict immunotherapy response in head and neck cancer. Clin Cancer Res 28, 2094–2109 (2022).
pubmed: 35262677 pmcid: 9161438 doi: 10.1158/1078-0432.CCR-21-3570
Peltier, A., Seban, R. D., Buvat, I., Bidard, F. C. & Mechta-Grigoriou, F. Fibroblast heterogeneity in solid tumors: from single cell analysis to whole-body imaging. Semin. Cancer Biol. 86, 262–272 (2022).
pubmed: 35489628 doi: 10.1016/j.semcancer.2022.04.008
Wu, S. Z. et al. A single-cell and spatially resolved atlas of human breast cancers. Nat. Genet. 53, 1334–1347 (2021).
pubmed: 34493872 pmcid: 9044823 doi: 10.1038/s41588-021-00911-1
Krishnamurty, A. T. et al. LRRC15(+) myofibroblasts dictate the stromal setpoint to suppress tumour immunity. Nature 611, 148–154 (2022).
pubmed: 36171287 pmcid: 9630141 doi: 10.1038/s41586-022-05272-1
Bhattacharjee, S. et al. Tumor restriction by type I collagen opposes tumor-promoting effects of cancer-associated fibroblasts. J. Clin. Invest. 131, e146987 (2021).
pubmed: 33905375 pmcid: 8159701 doi: 10.1172/JCI146987
Nicolas, A. M. et al. Inflammatory fibroblasts mediate resistance to neoadjuvant therapy in rectal cancer. Cancer Cell 40, 168–184.e113 (2022).
pubmed: 35120600 doi: 10.1016/j.ccell.2022.01.004
Pavkovic, M. et al. Multi omics analysis of fibrotic kidneys in two mouse models. Sci. Data 6, 92 (2019).
pubmed: 31201317 pmcid: 6570759 doi: 10.1038/s41597-019-0095-5
Naba, A. et al. Characterization of the extracellular matrix of normal and diseased tissues using proteomics. J. Proteome Res. 16, 3083–3091 (2017).
pubmed: 28675934 pmcid: 8078728 doi: 10.1021/acs.jproteome.7b00191
Chu, T., Wang, Z., Pe’er, D. & Danko, C. G. Cell type and gene expression deconvolution with BayesPrism enables Bayesian integrative analysis across bulk and single-cell RNA sequencing in oncology. Nat. Cancer 3, 505–517 (2022).
pubmed: 35469013 pmcid: 9046084 doi: 10.1038/s43018-022-00356-3
Forbes, M. S. et al. Fight-or-flight: murine unilateral ureteral obstruction causes extensive proximal tubular degeneration, collecting duct dilatation, and minimal fibrosis. Am. J. Physiol. Renal Physiol. 303, F120–F129 (2012).
pubmed: 22535799 pmcid: 3431140 doi: 10.1152/ajprenal.00110.2012
Conway, B. R. et al. Kidney single-cell atlas reveals myeloid heterogeneity in progression and regression of kidney disease. J. Am. Soc. Nephrol. 31, 2833–2854 (2020).
pubmed: 32978267 pmcid: 7790206 doi: 10.1681/ASN.2020060806
Grande, M. T. et al. Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease. Nat. Med. 21, 989–997 (2015).
pubmed: 26236989 doi: 10.1038/nm.3901
Lovisa, S. et al. Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis. Nat. Med. 21, 998–1009 (2015).
pubmed: 26236991 pmcid: 4587560 doi: 10.1038/nm.3902
Guiteras, R., Flaquer, M. & Cruzado, J. M. Macrophage in chronic kidney disease. Clin. Kidney J. 9, 765–771 (2016).
pubmed: 27994852 pmcid: 5162417 doi: 10.1093/ckj/sfw096
Tang, P. M., Nikolic-Paterson, D. J. & Lan, H. Y. Macrophages: versatile players in renal inflammation and fibrosis. Nat. Rev. Nephrol. 15, 144–158 (2019).
pubmed: 30692665 doi: 10.1038/s41581-019-0110-2
Wang, X. et al. The role of macrophages in kidney fibrosis. Front. Physiol. 12, 705838 (2021).
pubmed: 34421643 pmcid: 8378534 doi: 10.3389/fphys.2021.705838
Bell, R. M. B. & Conway, B. R. Macrophages in the kidney in health, injury and repair. Int. Rev. Cell Mol. Biol. 367, 101–147 (2022).
pubmed: 35461656 doi: 10.1016/bs.ircmb.2022.01.005
Vlasschaert, C., Moran, S. M. & Rauh, M. J. The myeloid-kidney interface in health and disease. Clin. J. Am. Soc. Nephrol. 17, 323–331 (2022).
pubmed: 34507968 pmcid: 8823925 doi: 10.2215/CJN.04120321
Casanova-Acebes, M. et al. Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells. Nature 595, 578–584 (2021).
pubmed: 34135508 pmcid: 8923521 doi: 10.1038/s41586-021-03651-8
Nalio Ramos, R. et al. Tissue-resident FOLR2(+) macrophages associate with CD8(+) T cell infiltration in human breast cancer. Cell 185, 1189–1207.e1125 (2022).
pubmed: 35325594 doi: 10.1016/j.cell.2022.02.021
Timperi, E. et al. Lipid-associated macrophages are induced by cancer-associated fibroblasts and mediate immune suppression in breast cancer. Cancer Res. 82, 3291–3306 (2022).
pubmed: 35862581 doi: 10.1158/0008-5472.CAN-22-1427
Zimmerman, K. A. et al. Single-cell RNA sequencing identifies candidate renal resident macrophage gene expression signatures across species. J. Am. Soc. Nephrol. 30, 767–781 (2019).
pubmed: 30948627 pmcid: 6493978 doi: 10.1681/ASN.2018090931
Fu, J. et al. The single-cell landscape of kidney immune cells reveals transcriptional heterogeneity in early diabetic kidney disease. Kidney Int. 102, 1291–1304 (2022).
pubmed: 36108806 pmcid: 9691617 doi: 10.1016/j.kint.2022.08.026
Kleshchevnikov, V. et al. Cell2location maps fine-grained cell types in spatial transcriptomics. Nat. Biotechnol. 40, 661–671 (2022).
pubmed: 35027729 doi: 10.1038/s41587-021-01139-4
Doke, T. et al. Single-cell analysis identifies the interaction of altered renal tubules with basophils orchestrating kidney fibrosis. Nat. Immunol. 23, 947–959 (2022).
pubmed: 35552540 doi: 10.1038/s41590-022-01200-7
Wu, H. et al. Mapping the single-cell transcriptomic response of murine diabetic kidney disease to therapies. Cell Metab. 34, 1064–1078.e1066 (2022).
pubmed: 35709763 pmcid: 9262852 doi: 10.1016/j.cmet.2022.05.010
O’Sullivan, E. D. et al. Indian Hedgehog release from TNF-activated renal epithelia drives local and remote organ fibrosis. Sci. Transl. Med. 15, eabn0736 (2023).
pubmed: 37256934 doi: 10.1126/scitranslmed.abn0736
Wu, X. et al. CXCL12/CXCR4: an amazing challenge and opportunity in the fight against fibrosis. Ageing Res. Rev. 83, 101809 (2023).
pubmed: 36442720 doi: 10.1016/j.arr.2022.101809
Van Damme, J. et al. Homogeneous interferon-inducing 22K factor is related to endogenous pyrogen and interleukin-1. Nature 314, 266–268 (1985).
pubmed: 3920526 doi: 10.1038/314266a0
Lemos, D. R. et al. Interleukin-1beta activates a MYC-dependent metabolic switch in kidney stromal cells necessary for progressive tubulointerstitial fibrosis. J. Am. Soc. Nephrol. 29, 1690–1705 (2018).
pubmed: 29739813 pmcid: 6054344 doi: 10.1681/ASN.2017121283
Lin, H. et al. Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science 320, 807–811 (2008).
pubmed: 18467591 doi: 10.1126/science.1154370
Mak, K. M. & Mei, R. Basement membrane type IV collagen and laminin: an overview of their biology and value as fibrosis biomarkers of liver disease. Anat. Rec. (Hoboken) 300, 1371–1390 (2017).
pubmed: 28187500 doi: 10.1002/ar.23567
Vu, R. et al. Wound healing in aged skin exhibits systems-level alterations in cellular composition and cell-cell communication. Cell Rep. 40, 111155 (2022).
pubmed: 35926463 pmcid: 9901190 doi: 10.1016/j.celrep.2022.111155
Garcia-Alonso, L., Holland, C. H., Ibrahim, M. M., Turei, D. & Saez-Rodriguez, J. Benchmark and integration of resources for the estimation of human transcription factor activities. Genome Res. 29, 1363–1375 (2019).
pubmed: 31340985 pmcid: 6673718 doi: 10.1101/gr.240663.118
Cao, J. et al. The single-cell transcriptional landscape of mammalian organogenesis. Nature 566, 496–502 (2019).
pubmed: 30787437 pmcid: 6434952 doi: 10.1038/s41586-019-0969-x
Han, H. et al. TRRUST: a reference database of human transcriptional regulatory interactions. Sci. Rep. 5, 11432 (2015).
pubmed: 26066708 pmcid: 4464350 doi: 10.1038/srep11432
Lin, S. L. et al. Macrophage Wnt7b is critical for kidney repair and regeneration. Proc. Natl. Acad. Sci. USA 107, 4194–4199 (2010).
pubmed: 20160075 pmcid: 2840080 doi: 10.1073/pnas.0912228107
Saha, S. et al. Macrophage-derived extracellular vesicle-packaged WNTs rescue intestinal stem cells and enhance survival after radiation injury. Nat. Commun. 7, 13096 (2016).
pubmed: 27734833 pmcid: 5065628 doi: 10.1038/ncomms13096
Gadegbeku, C. A. et al. Design of the Nephrotic Syndrome Study Network (NEPTUNE) to evaluate primary glomerular nephropathy by a multidisciplinary approach. Kidney Int 83, 749–756 (2013).
pubmed: 23325076 pmcid: 3612359 doi: 10.1038/ki.2012.428
Gillies, C. E. et al. An eQTL landscape of kidney tissue in human nephrotic syndrome. Am. J. Hum. Genet. 103, 232–244 (2018).
pubmed: 30057032 pmcid: 6081280 doi: 10.1016/j.ajhg.2018.07.004
Anders, H. J. & Ryu, M. Renal microenvironments and macrophage phenotypes determine progression or resolution of renal inflammation and fibrosis. Kidney Int. 80, 915–925 (2011).
pubmed: 21814171 doi: 10.1038/ki.2011.217
Ricardo, S. D., van Goor, H. & Eddy, A. A. Macrophage diversity in renal injury and repair. J. Clin. Invest. 118, 3522–3530 (2008).
pubmed: 18982158 pmcid: 2575702 doi: 10.1172/JCI36150
Muto, Y. et al. Defining cellular complexity in human autosomal dominant polycystic kidney disease by multimodal single cell analysis. Nat. Commun. 13, 6497 (2022).
pubmed: 36310237 pmcid: 9618568 doi: 10.1038/s41467-022-34255-z
Henderson, N. C., Rieder, F. & Wynn, T. A. Fibrosis: from mechanisms to medicines. Nature 587, 555–566 (2020).
pubmed: 33239795 pmcid: 8034822 doi: 10.1038/s41586-020-2938-9
Affo, S. et al. Promotion of cholangiocarcinoma growth by diverse cancer-associated fibroblast subpopulations. Cancer Cell 39, 866–882.e811 (2021).
pubmed: 33930309 pmcid: 8241235 doi: 10.1016/j.ccell.2021.03.012
Chang, S. K. et al. Cadherin-11 regulates fibroblast inflammation. Proc. Natl. Acad. Sci. USA 108, 8402–8407 (2011).
pubmed: 21536877 pmcid: 3100978 doi: 10.1073/pnas.1019437108
Croft, A. P. et al. Distinct fibroblast subsets drive inflammation and damage in arthritis. Nature 570, 246–251 (2019).
pubmed: 31142839 pmcid: 6690841 doi: 10.1038/s41586-019-1263-7
Mhaidly, R. & Mechta-Grigoriou, F. Role of cancer-associated fibroblast subpopulations in immune infiltration, as a new means of treatment in cancer. Immunol. Rev. 302, 259–272 (2021).
pubmed: 34013544 pmcid: 8360036 doi: 10.1111/imr.12978
Wei, K., Nguyen, H. N. & Brenner, M. B. Fibroblast pathology in inflammatory diseases. J. Clin. Invest. 131, e149538 (2021).
pubmed: 34651581 pmcid: 8516469 doi: 10.1172/JCI149538
Mizoguchi, F. et al. Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis. Nat. Commun. 9, 789 (2018).
pubmed: 29476097 pmcid: 5824882 doi: 10.1038/s41467-018-02892-y
Zhang, F. et al. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat. Immunol. 20, 928–942 (2019).
pubmed: 31061532 pmcid: 6602051 doi: 10.1038/s41590-019-0378-1
Cantero-Navarro, E. et al. Role of macrophages and related cytokines in kidney disease. Front. Med. 8, 688060 (2021).
doi: 10.3389/fmed.2021.688060
Cassetta, L. et al. Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers, and therapeutic targets. Cancer Cell 35, 588–602.e510 (2019).
pubmed: 30930117 pmcid: 6472943 doi: 10.1016/j.ccell.2019.02.009
Kawakami, T., Ren, S. & Duffield, J. S. Wnt signalling in kidney diseases: dual roles in renal injury and repair. J. Pathol. 229, 221–231 (2013).
pubmed: 23097132 doi: 10.1002/path.4121
Xiao, L. et al. Sustained activation of Wnt/β-catenin signaling drives AKI to CKD progression. J. Am. Soc. Nephrol. 27, 1727–1740 (2016).
pubmed: 26453613 doi: 10.1681/ASN.2015040449
Zuo, Y. & Liu, Y. New insights into the role and mechanism of Wnt/β-catenin signalling in kidney fibrosis. Nephrology 23, 38–43 (2018).
pubmed: 30298654 doi: 10.1111/nep.13472
Malik, S. A., Modarage, K. & Goggolidou, P. The Role of Wnt Signalling in Chronic Kidney Disease (CKD). Genes 11, 496 (2020).
pubmed: 32365994 pmcid: 7290783 doi: 10.3390/genes11050496
Schunk, S. J., Floege, J., Fliser, D. & Speer, T. WNT-β-catenin signalling—a versatile player in kidney injury and repair. Nat. Rev. Nephrol. 17, 172–184 (2021).
pubmed: 32989282 doi: 10.1038/s41581-020-00343-w
Li, L., Fu, H. & Liu, Y. The fibrogenic niche in kidney fibrosis: components and mechanisms. Nat. Rev. Nephrol. 18, 545–557 (2022).
pubmed: 35788561 doi: 10.1038/s41581-022-00590-z
Zhou, D. et al. Fibroblast-specific β-catenin signaling dictates the outcome of AKI. J. Am. Soc. Nephrol. 29, 1257–1271 (2018).
pubmed: 29343518 pmcid: 5875957 doi: 10.1681/ASN.2017080903
Zhou, D. et al. Tubule-derived Wnts are required for fibroblast activation and kidney fibrosis. J. Am. Soc. Nephrol. 28, 2322–2336 (2017).
pubmed: 28336721 pmcid: 5533232 doi: 10.1681/ASN.2016080902
Surendran, K., Schiavi, S. & Hruska, K. A. Wnt-dependent beta-catenin signaling is activated after unilateral ureteral obstruction, and recombinant secreted frizzled-related protein 4 alters the progression of renal fibrosis. J. Am. Soc. Nephrol. 16, 2373–2384 (2005).
pubmed: 15944336 doi: 10.1681/ASN.2004110949
Feng, Y. et al. Wnt/β-catenin-promoted macrophage alternative activation contributes to kidney fibrosis. J. Am. Soc. Nephrol. 29, 182–193 (2018).
pubmed: 29021383 doi: 10.1681/ASN.2017040391
Ju, W. et al. Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker. Sci. Transl. Med. 7, 316ra193 (2015).
pubmed: 26631632 pmcid: 4861144 doi: 10.1126/scitranslmed.aac7071
Barisoni, L. et al. Digital pathology evaluation in the multicenter Nephrotic Syndrome Study Network (NEPTUNE). Clin. J. Am. Soc. Nephrol. 8, 1449–1459 (2013).
pubmed: 23393107 pmcid: 3731905 doi: 10.2215/CJN.08370812
Hao, Y. et al. Integrated analysis of multimodal single-cell data. Cell 184, 3573–3587.e3529 (2021).
pubmed: 34062119 pmcid: 8238499 doi: 10.1016/j.cell.2021.04.048
Cohen, C. D., Frach, K., Schlondorff, D. & Kretzler, M. Quantitative gene expression analysis in renal biopsies: a novel protocol for a high-throughput multicenter application. Kidney Int. 61, 133–140 (2002).
pubmed: 11786093 doi: 10.1046/j.1523-1755.2002.00113.x
Zee, J. et al. Kidney biopsy features most predictive of clinical outcomes in the spectrum of minimal change disease and focal segmental glomerulosclerosis. J. Am. Soc. Nephrol. 33, 1411–1426 (2022).
pubmed: 35581011 pmcid: 9257823 doi: 10.1681/ASN.2021101396

Auteurs

Camille Cohen (C)

Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France.
Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France.

Rana Mhaidly (R)

Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France.
Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France.

Hugo Croizer (H)

Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France.
Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France.

Yann Kieffer (Y)

Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France.
Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France.

Renaud Leclere (R)

Department of Diagnostic and Theragnostic Medicine, Institut Curie Hospital Group, 26, rue d'Ulm, F-75248, Paris, France.

Anne Vincent-Salomon (A)

Department of Diagnostic and Theragnostic Medicine, Institut Curie Hospital Group, 26, rue d'Ulm, F-75248, Paris, France.

Catherine Robley (C)

Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France.
Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France.

Dany Anglicheau (D)

Department of Nephrology and Kidney Transplantation, Necker Hospital, AP-HP, Paris Cité University, Inserm U1151, 149 rue de Sèvres, 75015, Paris, France.

Marion Rabant (M)

Department of Pathology, Necker Hospital, AP-HP, Paris Cité University, 149 rue de Sèvres, 75015, Paris, France.

Aurélie Sannier (A)

Department of Pathology, AP-HP, Bichat-Claude Bernard Hospital, Paris Cité University, Inserm, U1148, 46, rue Henri Huchard, 75877, Paris, France.

Marc-Olivier Timsit (MO)

Department of Urology, Européen George Pompidou Hospital, APHP, Paris Cité University, Paris, France.

Sean Eddy (S)

Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.

Matthias Kretzler (M)

Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.

Wenjun Ju (W)

Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, 48109, USA.

Fatima Mechta-Grigoriou (F)

Institut Curie, Stress and Cancer Laboratory, Equipe labélisée par la Ligue Nationale contre le Cancer, PSL Research University, 26, rue d'Ulm, F-75248, Paris, France. fatima.mechta-grigoriou@curie.fr.
Inserm, U830, 26, rue d'Ulm, Paris, F-75005, France. fatima.mechta-grigoriou@curie.fr.

Classifications MeSH