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The Mesangial cell — the glomerular stromal cell

Nature Reviews Nephrology volume 17, pages 855–864 (2021)Cite this article

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Abstract

Mesangial cells are stromal cells that are important for kidney glomerular homeostasis and the glomerular response to injury. A growing body of evidence demonstrates that mesenchymal stromal cells, such as stromal fibroblasts, pericytes and vascular smooth muscle cells, not only specify the architecture of tissues but also regulate developmental processes, vascularization and cell fate specification. In addition, through crosstalk with neighbouring cells and indirectly through the remodelling of the matrix, stromal cells can regulate a variety of processes such as immunity, inflammation, regeneration and in the context of maladaptive responses — fibrosis. Insights into the molecular phenotype of kidney mesangial cells suggest that they are a specialized stromal cell of the glomerulus. Here, we review our current understanding of mesenchymal stromal cells and discuss how it informs the function of mesangial cells and their role in disease. These new insights could lead to a better understanding of kidney disease pathogenesis and the development of new therapies for chronic kidney disease.

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Fig. 1: Proposed functions of stromal cells.
Fig. 2: Stromal and immune cell organization and interactions in the lymph node.
Fig. 3: Glomerular structure and main cell types in steady state and disease.

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References

  1. Zimmerman, K. Uber den Bau des Glomerulus der Slugerniere. Ztschr. f. mik-anat. Forsch 32, 176–277 (1933).

    Google Scholar 

  2. Farquhar, M. G. & Palade, G. E. Functional evidence for the existence of a third cell type in the renal glomerulus: phagocytosis of filtration residues by a distinctive ‘third’ cell. J. Cell Biol. 13, 55–87 (1962).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Kimmelstiel, P. & Wilson, C. Intercapillary lesions in the glomeruli of the kidney. Am. J. Pathol. 12, 83–98.7 (1936).

    PubMed  PubMed Central  CAS  Google Scholar 

  4. Cattell, V. & Bradfield, J. W. Focal mesangial proliferative glomerulonephritis in the rat caused by habu snake venom. A morphologic study. Am. J. Pathol. 87, 511–524 (1977).

    PubMed  PubMed Central  CAS  Google Scholar 

  5. Rosenmann, E. & Eliakim, M. Nephrotic syndrome associated with amyloid-like glomerular deposits. Nephron 18, 301–308 (1977).

    Article  PubMed  CAS  Google Scholar 

  6. Churg, J. & Grishman, E. Ultrastructure of immune deposits in renal glomeruli. Ann. Intern. Med. 76, 479–486 (1972).

    Article  PubMed  CAS  Google Scholar 

  7. Schlöndorff, D. & Banas, B. The mesangial cell revisited: no cell is an island. J Am. Soc. Nephrol. 20, 1179–1187 (2009).

    Article  PubMed  Google Scholar 

  8. Ruotsalainen, V. et al. Nephrin is specifically located at the slit diaphragm of glomerular podocytes. Proc. Natl Acad. Sci. USA 96, 7962–7967 (1999).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Shih, N.-Y. et al. Congenital nephrotic syndrome in mice lacking CD2-sssociated protein. Science 286, 312–315 (1999).

    Article  PubMed  CAS  Google Scholar 

  10. Boute, N. et al. NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat. Genet. 24, 349–354 (2000).

    Article  PubMed  CAS  Google Scholar 

  11. Rodewald, R. & Karnovsky, M. J. Porous substructure of the glomerular slit diaphragm in the rat and mouse. J. Cell Biol. 60, 423–433 (1974).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Kriz, W. Progressive renal failure — inability of podocytes to replicate and the consequences for development of glomerulosclerosis. Nephrol. Dial. Transpl. 11, 1738–1742 (1996).

    CAS  Google Scholar 

  13. Kitching, A. R. & Hutton, H. L. The players: cells involved in glomerular disease. Clin. J. Am. Soc. Nephrol. 11, 1664–1674 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Chung, J.-J. et al. Single-cell transcriptome profiling of the kidney glomerulus identifies key cell types and reactions to injury. J. Am. Soc. Nephrol. 31, 2341–2354 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Koliaraki, V., Prados, A., Armaka, M. & Kollias, G. The mesenchymal context in inflammation, immunity and cancer. Nat. Immunol. 21, 974–982 (2020).

    Article  PubMed  CAS  Google Scholar 

  16. Navarro-González, J. F., Mora-Fernández, C., Muros de Fuentes, M. & García-Pérez, J. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat. Rev. Nephrol. 7, 327–340 (2011).

    Article  PubMed  Google Scholar 

  17. Costantini, F. & Kopan, R. Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development. Dev. Cell 18, 698–712 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Bonnans, C., Chou, J. & Werb, Z. Remodelling the extracellular matrix in development and disease. Nat. Rev. Mol. Cell Biol. 15, 786–801 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Song, B. et al. The directed differentiation of human iPS cells into kidney podocytes. PLoS ONE 7, e46453 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Ott, H. C. et al. Perfusion-decellularized matrix: using nature’s platform to engineer a bioartificial heart. Nat. Med. 14, 213–221 (2008).

    Article  PubMed  CAS  Google Scholar 

  21. García-Gareta, E. et al. Decellularised scaffolds: just a framework? Current knowledge and future directions. J. Tissue Eng. 11, 2041731420942903 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).

    Article  PubMed  CAS  Google Scholar 

  23. Stupack, D. G. & Cheresh, D. A. ECM remodeling regulates angiogenesis: endothelial integrins look for new ligands. Sci. STKE 2002, pe7–pe7 (2002).

    Article  PubMed  Google Scholar 

  24. Bissell, M. J., Hall, H. G. & Parry, G. How does the extracellular matrix direct gene expression? J. Theor. Biol. 99, 31–68 (1982).

    Article  PubMed  CAS  Google Scholar 

  25. Lu, P., Takai, K., Weaver, V. M. & Werb, Z. Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb. Perspect. Biol. 3, a005058 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Hynes, R. O. Extracellular matrix: not just pretty fibrils. Science 326, 1216–1219 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Halder, G., Dupont, S. & Piccolo, S. Transduction of mechanical and cytoskeletal cues by YAP and TAZ. Nat. Rev. Mol. Cell Biol. 13, 591–600 (2012).

    Article  PubMed  CAS  Google Scholar 

  28. Dupont, S. et al. Role of YAP/TAZ in mechanotransduction. Nature 474, 179–183 (2011).

    Article  PubMed  CAS  Google Scholar 

  29. Yu, H., Mouw, J. K. & Weaver, V. M. Forcing form and function: biomechanical regulation of tumor evolution. Trends Cell Biol. 21, 47–56 (2011).

    Article  PubMed  Google Scholar 

  30. Sims, D. E. The pericyte — a review. Tissue Cell 18, 153–174 (1986).

    Article  PubMed  CAS  Google Scholar 

  31. Cho, H., Kozasa, T., Bondjers, C., Betsholtz, C. & Kehrl, J. H. Pericyte-specific expression of Rgs5: implications for PDGF and EDG receptor signaling during vascular maturation. FASEB J. 17, 1–17 (2003).

    Article  Google Scholar 

  32. Naba, A. et al. The extracellular matrix: tools and insights for the ‘omics’ era. Matrix Biol. 49, 10–24 (2016).

    Article  PubMed  CAS  Google Scholar 

  33. LeBleu, V. S. & Neilson, E. G. Origin and functional heterogeneity of fibroblasts. FASEB J. 34, 3519–3536 (2020).

    Article  PubMed  CAS  Google Scholar 

  34. Frantz, C., Stewart, K. M. & Weaver, V. M. The extracellular matrix at a glance. J. Cell Sci. 123, 4195–4200 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Maxson, S., Lopez, E. A., Yoo, D., Danilkovitch-Miagkova, A. & Leroux, M. A. Concise review: role of mesenchymal stem cells in wound repair. Stem Cell Transl Med. 1, 142–149 (2012).

    Article  CAS  Google Scholar 

  36. Griffin, M. F., desJardins-Park, H. E., Mascharak, S., Borrelli, M. R. & Longaker, M. T. Understanding the impact of fibroblast heterogeneity on skin fibrosis. Dis. Models Mech. 13, dmm044164 (2020).

    Article  CAS  Google Scholar 

  37. Richman, P. I., Tilly, R., Jass, J. R. & Bodmer, W. F. Colonic pericrypt sheath cells: characterisation of cell type with new monoclonal antibody. J. Clin. Pathol. 40, 593–600 (1987).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Eyden, B., Curry, A. & Wang, G. Stromal cells in the human gut show ultrastructural features of fibroblasts and smooth muscle cells but not myofibroblasts. J. Cell. Mol. Med. 15, 1483–1491 (2011).

    Article  PubMed  Google Scholar 

  39. Desmoulière, A., Geinoz, A., Gabbiani, F. & Gabbiani, G. Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J. Cell Biol. 122, 103–111 (1993).

    Article  PubMed  Google Scholar 

  40. Hinz, B. et al. Recent developments in myofibroblast biology: paradigms for connective tissue remodeling. Am. J. Pathol. 180, 1340–1355 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Pakshir, P. et al. The myofibroblast at a glance. J. Cell Sci. 133, jcs227900 (2020).

    Article  PubMed  CAS  Google Scholar 

  42. Buechler, M. B. et al. Cross-tissue organization of the fibroblast lineage. Nature 593, 575–579 (2021).

    Article  PubMed  CAS  Google Scholar 

  43. Owens, B. M. J. Inflammation, innate immunity, and the intestinal stromal cell niche: opportunities and challenges. Front. Immunol. 6, 319 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Nowarski, R., Jackson, R. & Flavell, R. A. The stromal intervention: regulation of immunity and inflammation at the epithelial-mesenchymal barrier. Cell 168, 362–375 (2017).

    Article  PubMed  CAS  Google Scholar 

  45. Meier, B. et al. Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-α. Biochem. J. 263, 539–545 (1989).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Sundaresan, M. et al. Regulation of reactive-oxygen-species generation in fibroblasts by Rac1. Biochem. J. 318, 379–382 (1996).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Krausgruber, T. et al. Structural cells are key regulators of organ-specific immune responses. Nature 583, 296–302 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Doppler, S. A. et al. Cardiac fibroblasts: more than mechanical support. J. Thorac. Dis. 9, S36–S51 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Humeres, C. & Frangogiannis, N. G. Fibroblasts in the infarcted, remodeling, and failing heart. JACC Basic Transl Sci. 4, 449–467 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Wilson, M. S. & Wynn, T. A. Pulmonary fibrosis: pathogenesis, etiology and regulation. Mucosal Immunol. 2, 103–121 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Wynn, T. A. & Vannella, K. M. Macrophages in tissue repair, regeneration, and fibrosis. Immunity 44, 450–462 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Jiang, H., Hegde, S. & DeNardo, D. G. Tumor-associated fibrosis as a regulator of tumor immunity and response to immunotherapy. Cancer Immunol. Immunother. 66, 1037–1048 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Krishnamurty, A. T. & Turley, S. J. Lymph node stromal cells: cartographers of the immune system. Nat. Immunol. 21, 369–380 (2020).

    Article  PubMed  CAS  Google Scholar 

  54. Perez-Shibayama, C., Gil-Cruz, C. & Ludewig, B. Fibroblastic reticular cells at the nexus of innate and adaptive immune responses. Immunol. Rev. 289, 31–41 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Kalluri, R. The biology and function of fibroblasts in cancer. Nat. Rev. Cancer 16, 582–598 (2016).

    Article  PubMed  CAS  Google Scholar 

  56. Sahai, E. et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat. Rev. Cancer 20, 174–186 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Turley, S. J., Cremasco, V. & Astarita, J. L. Immunological hallmarks of stromal cells in the tumour microenvironment. Nat. Rev. Immunol. 15, 669–682 (2015).

    Article  PubMed  CAS  Google Scholar 

  58. Vitale, I., Shema, E., Loi, S. & Galluzzi, L. Intratumoral heterogeneity in cancer progression and response to immunotherapy. Nat. Med. 27, 212–224 (2021).

    Article  PubMed  CAS  Google Scholar 

  59. Kalluri, R. & Zeisberg, M. Fibroblasts in cancer. Nat. Rev. Cancer 6, 392–401 (2006).

    Article  PubMed  CAS  Google Scholar 

  60. Kalluri, R. & Weinberg, R. A. The basics of epithelial-mesenchymal transition. J. Clin. Invest. 119, 1420–1428 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Armulik, A., Genové, G. & Betsholtz, C. Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev. Cell 21, 193–215 (2011).

    Article  PubMed  CAS  Google Scholar 

  62. Lemley, K. V. & Kriz, W. Anatomy of the renal interstitium. Kidney Int. 39, 370–381 (1991).

    Article  PubMed  CAS  Google Scholar 

  63. Kuppe, C. et al. Decoding myofibroblast origins in human kidney fibrosis. Nature 589, 281–286 (2021).

    Article  PubMed  CAS  Google Scholar 

  64. Kobayashi, A. et al. Identification of a multipotent self-renewing stromal progenitor population during mammalian kidney organogenesis. Stem Cell Rep. 3, 650–662 (2014).

    Article  CAS  Google Scholar 

  65. Levinson, R. S. et al. Foxd1-dependent signals control cellularity in the renal capsule, a structure required for normal renal development. Development 132, 529–539 (2005).

    Article  PubMed  CAS  Google Scholar 

  66. Bohnenpoll, T. et al. Tbx18 expression demarcates multipotent precursor populations in the developing urogenital system but is exclusively required within the ureteric mesenchymal lineage to suppress a renal stromal fate. Dev. Biol. 380, 25–36 (2013).

    Article  PubMed  CAS  Google Scholar 

  67. England, A. R. et al. Identification and characterization of cellular heterogeneity within the developing renal interstitium. Development 147, dev190108 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Fetting, J. L. et al. FOXD1 promotes nephron progenitor differentiation by repressing decorin in the embryonic kidney. Development 141, 17–27 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Oxburgh, L., Brown, A. C., Muthukrishnan, S. D. & Fetting, J. L. Bone morphogenetic protein signaling in nephron progenitor cells. Pediatr. Nephrol. 29, 531–536 (2014).

    Article  PubMed  Google Scholar 

  70. Das, A. et al. Stromal-epithelial crosstalk regulates kidney progenitor cell differentiation. Nat. Cell Biol. 15, 1035–1044 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Batourina, E. et al. Vitamin A controls epithelial/mesenchymal interactions through Ret expression. Nat. Genet. 27, 74–78 (2001).

    Article  PubMed  CAS  Google Scholar 

  72. Hurtado, R. et al. Pbx1-dependent control of VMC differentiation kinetics underlies gross renal vascular patterning. Development 142, 2653–2664 (2015).

    PubMed  PubMed Central  CAS  Google Scholar 

  73. Sequeira-Lopez, M. L. S. et al. The earliest metanephric arteriolar progenitors and their role in kidney vascular development. Am. J. Physiol. Regul. Integr. Comp. Physiol. 308, R138–R149 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Tobian, L. Relationship of juxtaglomerular apparatus to renin and angiotensin. Circulation 25, 189–192 (1962).

    Article  PubMed  CAS  Google Scholar 

  75. Faarup, P. Renin location in the different parts of the juxtaglomerular apparatus in the cat kidney. 2. Fractions of the afferent arteriole, the cell group of Goormaghtigh, the efferent arteriole and the glomerulus. Acta Pathol. Microbiol. Scand. 72, 109–117 (1968).

    Article  PubMed  CAS  Google Scholar 

  76. Sequeira Lopez, M. L., Pentz, E. S., Robert, B., Abrahamson, D. R. & Gomez, R. A. Embryonic origin and lineage of juxtaglomerular cells. Am. J. Physiol. Renal Physiol. 281, F345–F356 (2001).

    Article  PubMed  CAS  Google Scholar 

  77. Zangheri, E. O. et al. Production of erythropoietin by anoxic perfusion of the isolated kidney of a dog. Nature 199, 572–573 (1963).

    Article  PubMed  CAS  Google Scholar 

  78. Kaelin, W. G. & Ratcliffe, P. J. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol. Cell 30, 393–402 (2008).

    Article  PubMed  CAS  Google Scholar 

  79. Semenza, G. L. Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology. Annu. Rev. Pathol. 9, 47–71 (2014).

    Article  PubMed  CAS  Google Scholar 

  80. Koury, M. J. & Haase, V. H. Anaemia in kidney disease: harnessing hypoxia responses for therapy. Nat. Rev. Nephrol. 11, 394–410 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Cooper, W. M. & Tuttle, W. B. Polycythemia associated with a benign kidney lesion: report of a case of erythrocytosis with hydronephrosis, with remission of polycythemia following nephrectomy. Ann. Intern. Med. 47, 1008–1015 (1957).

    Article  PubMed  CAS  Google Scholar 

  82. Conley, C. L., Kowal, J. & D’antonio, J. Polycythemia associated with renal tumors. Bull. Johns. Hopkins Hosp. 101, 63–73 (1957).

    PubMed  CAS  Google Scholar 

  83. Kramann, R. et al. Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis. Cell Stem Cell 16, 51–66 (2015).

    Article  PubMed  CAS  Google Scholar 

  84. LeBleu, V. S. et al. Origin and function of myofibroblasts in kidney fibrosis. Nat. Med. 19, 1047–1053 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Boyle, S. C., Liu, Z. & Kopan, R. Notch signaling is required for the formation of mesangial cells from a stromal mesenchyme precursor during kidney development. Development 141, 346–354 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Brunskill, E. W. & Potter, S. S. Changes in the gene expression programs of renal mesangial cells during diabetic nephropathy. BMC Nephrol 13, 70 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  87. He, B. et al. Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes. Nat. Commun. 12, 2141 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Der, E. et al. Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways. Nat. Immunol. 20, 915–927 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Karaiskos, N. et al. A single-cell transcriptome atlas of the mouse glomerulus. J. Am. Soc. Nephrol. 29, 2060–2068 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Park, J. et al. Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease. Science 360, 758–763 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Korin, B., Chung, J.-J., Avraham, S. & Shaw, A. S. Preparation of single-cell suspensions of mouse glomeruli for high-throughput analysis. Nat. Protoc. 16, 4068–4083 (2021).

    Article  PubMed  CAS  Google Scholar 

  92. Pricam, C., Humbert, F., Perrelet, A. & Orci, L. GAP junctions in mesangial and lacis cells. J. Cell Biol. 63, 349–354 (1974).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Hugo, C., Shankland, S. J., Bowen-Pope, D. F., Couser, W. G. & Johnson, R. J. Extraglomerular origin of the mesangial cell after injury. A new role of the juxtaglomerular apparatus. J. Clin. Invest. 100, 786–794 (1997).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Chaudhari, S. et al. Inhibition of interleukin-6 on matrix protein production by glomerular mesangial cells and the pathway involved. Am. J. Physiol. Renal Physiol. 318, F1478–F1488 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Shotorbani, P. Y., Chaudhari, S., Tao, Y., Tsiokas, L. & Ma, R. Inhibitor of myogenic differentiation family isoform a, a new positive regulator of fibronectin production by glomerular mesangial cells. Am. J. Physiol. Renal Physiol. 318, F673–F682 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Bjarnegård, M. et al. Endothelium-specific ablation of PDGFB leads to pericyte loss and glomerular, cardiac and placental abnormalities. Development 131, 1847–1857 (2004).

    Article  PubMed  Google Scholar 

  97. Lindahl, P. et al. Paracrine PDGF-B/PDGF-Rbeta signaling controls mesangial cell development in kidney glomeruli. Development 125, 3313–3322 (1998).

    Article  PubMed  CAS  Google Scholar 

  98. Kikkawa, Y., Virtanen, I. & Miner, J. H. Mesangial cells organize the glomerular capillaries by adhering to the G domain of laminin alpha5 in the glomerular basement membrane. J. Cell Biol. 161, 187–196 (2003).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Morita, T. & Churg, J. Mesangiolysis. Kidney Int. 24, 1–9 (1983).

    Article  PubMed  CAS  Google Scholar 

  100. Suzuki, T. Experimentelle “Habu ”-Gift-Nephritis. Verh. Jpn. Pathol. Ges. 7, 84–87 (1917).

    Google Scholar 

  101. Kitamura, H. et al. The pathological study of “Habu”(Trimeresurus flavoridis) venom. II. The histopathological study of the rabbit renal lesions caused by intravenous inoculation of “Habu” venom. Med. J. Kagoshima. Univ. 9, 1586–1593 (1958).

    Google Scholar 

  102. Grigorieva, I. V. et al. A novel role for GATA3 in mesangial cells in glomerular development and injury. J. Am. Soc. Nephrol. 30, 1641–1658 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Nelson, T., Velazquez, H., Troiano, N. & Fretz, J. A. Early B cell factor 1 (EBF1) Regulates glomerular development by controlling mesangial maturation and consequently COX-2 expression. J. Am. Soc. Nephrol. 30, 1559–1572 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  104. Schreiner, G. F. The mesangial phagocyte and its regulation of contractile cell biology. J. Am. Soc. Nephrol. 2, S74–S82 (1992).

    Article  PubMed  CAS  Google Scholar 

  105. Baud, L. et al. Reactive oxygen production by cultured rat glomerular mesangial cells during phagocytosis is associated with stimulation of lipoxygenase activity. J. Exp. Med. 158, 1836–1852 (1983).

    Article  PubMed  CAS  Google Scholar 

  106. Johnson, R. J. et al. Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. Alpha-smooth muscle actin is a marker of mesangial cell proliferation. J. Clin. Invest. 87, 847–858 (1991).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. Farris, A. B. & Colvin, R. B. Renal interstitial fibrosis: mechanisms and evaluation. Curr. Opin. Nephrol. Hypertens. 21, 289–300 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Lin, S.-L., Kisseleva, T., Brenner, D. A. & Duffield, J. S. Pericytes and perivascular fibroblasts are the primary source of collagen-producing cells in obstructive fibrosis of the kidney. Am. J. Pathol. 173, 1617–1627 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Brosius, F. C. New insights into the mechanisms of fibrosis and sclerosis in diabetic nephropathy. Rev. Endocr. Metab. Disord. 9, 245–254 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Garcia-Fernandez, N. et al. Matrix metalloproteinases in diabetic kidney disease. J. Clin. Med. 9, 472 (2020).

    Article  PubMed Central  CAS  Google Scholar 

  111. Ludwig, C. H. & Bintu, L. Mapping chromatin modifications at the single cell level. Development 146, dev170217 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Gate, D. et al. Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer’s disease. Nature 577, 399–404 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Spitzer, M. H. & Nolan, G. P. Mass cytometry: single cells, many features. Cell 165, 780–791 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Basiji, D. & O’Gorman, M. R. G. Imaging flow cytometry. J. Immunol. Methods 423, 1–2 (2015).

    Article  PubMed  CAS  Google Scholar 

  115. Giesen, C. et al. Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry. Nat. Methods 11, 417–422 (2014).

    Article  PubMed  CAS  Google Scholar 

  116. Hartmann, F. J. & Bendall, S. C. Immune monitoring using mass cytometry and related high-dimensional imaging approaches. Nat. Rev. Rheumatol. 16, 87–99 (2020).

    Article  PubMed  Google Scholar 

  117. Abedini, A. et al. Urinary single-cell profiling captures the cellular diversity of the kidney. JASN 32, 614–627 (2021).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  118. Eddy, S., Mariani, L. H. & Kretzler, M. Integrated multi-omics approaches to improve classification of chronic kidney disease. Nat. Rev. Nephrol. 16, 657–668 (2020).

    Article  PubMed  Google Scholar 

  119. Liao, J. et al. Single-cell RNA sequencing of human kidney. Sci. Data 7, 4 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Kirita, Y., Wu, H., Uchimura, K., Wilson, P. C. & Humphreys, B. D. Cell profiling of mouse acute kidney injury reveals conserved cellular responses to injury. Proc. Natl Acad. Sci. USA 117, 15874–15883 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Park, J., Liu, C. L., Kim, J. & Susztak, K. Understanding the kidney one cell at a time. Kidney Int. 96, 862–870 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. Stuart, T. & Satija, R. Integrative single-cell analysis. Nat. Rev. Genet. 20, 257–272 (2019).

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We wish to dedicate this Perspective to the memory of D. Schlondorff who kept the memory of mesangial cells alive during the era of the podocyte. We also thank E. Unanue (Washington University in St Louis, MO, USA), J. Schraibman (Washington University in St Louis, MO, USA), and J. C. Marler (St Louis University, MO, USA) for investigating the origin of the word mesangium, and R. Kopan (Cincinnati Children’s Hospital Medical Center, OH, USA) for helpful discussions. This work was supported by Genentech.

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  1. These authors contributed equally: Shimrit Avraham, Ben Korin.

Authors and Affiliations

  1. Department of Research Biology, Genentech, South San Francisco, CA, USA

    Shimrit Avraham, Ben Korin & Andrey S. Shaw

  2. Pin Pharmaceuticals, South San Francisco, CA, USA

    Jun-Jae Chung

  3. The Rogosin Institute, New York, NY, USA

    Leif Oxburgh

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  1. Shimrit Avraham
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  2. Ben Korin
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  3. Jun-Jae Chung
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Contributions

S.A., B.K., L.O., and A.S.S. researched data for the article and reviewed and/or edited the manuscript before submission. All authors contributed substantially to discussion of the content and contributed to writing the article.

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Correspondence to Andrey S. Shaw.

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Competing interests

S.A., B.K. and A.S.S. are employees of Genentech Research and Early Development. J.-J.C. is an employee of Pin Pharmaceuticals. L.O. declares no competing interests.

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Nature Reviews Nephrology thanks J. Krepinsky, T. K. Nowling and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Avraham, S., Korin, B., Chung, JJ. et al. The Mesangial cell — the glomerular stromal cell. Nat Rev Nephrol 17, 855–864 (2021). https://doi.org/10.1038/s41581-021-00474-8

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