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SOX9 switch links regeneration to fibrosis at the single-cell level in mammalian kidneys.
Aggarwal, Shikhar; Wang, Zhanxiang; Rincon Fernandez Pacheco, David; Rinaldi, Anna; Rajewski, Alex; Callemeyn, Jasper; Van Loon, Elisabet; Lamarthée, Baptiste; Covarrubias, Ambart Ester; Hou, Jean; Yamashita, Michifumi; Akiyama, Haruhiko; Karumanchi, S Ananth; Svendsen, Clive N; Noble, Paul W; Jordan, Stanley C; Breunig, Joshua J; Naesens, Maarten; Cippà, Pietro E; Kumar, Sanjeev.
Afiliação
  • Aggarwal S; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Wang Z; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Rincon Fernandez Pacheco D; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Rinaldi A; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Rajewski A; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Callemeyn J; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Van Loon E; Division of Nephrology, Ente Ospedaliero Cantonale, CH-6900 Lugano, Switzerland.
  • Lamarthée B; Applied Genomics, Computation, and Translational Core, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Covarrubias AE; Department of Microbiology, Immunology and Transplantation, KU Leuven, BE-3000 Leuven, Belgium.
  • Hou J; Department of Microbiology, Immunology and Transplantation, KU Leuven, BE-3000 Leuven, Belgium.
  • Yamashita M; Department of Microbiology, Immunology and Transplantation, KU Leuven, BE-3000 Leuven, Belgium.
  • Akiyama H; Division of Nephrology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Karumanchi SA; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Svendsen CN; Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Noble PW; Department of Orthopaedic Surgery, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
  • Jordan SC; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Breunig JJ; Division of Nephrology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Naesens M; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Cippà PE; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Kumar S; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Science ; 383(6685): eadd6371, 2024 Feb 23.
Article em En | MEDLINE | ID: mdl-38386758
ABSTRACT
The steps governing healing with or without fibrosis within the same microenvironment are unclear. After acute kidney injury (AKI), injured proximal tubular epithelial cells activate SOX9 for self-restoration. Using a multimodal approach for a head-to-head comparison of injury-induced SOX9 lineages, we identified a dynamic SOX9 switch in repairing epithelia. Lineages that regenerated epithelia silenced SOX9 and healed without fibrosis (SOX9on-off). By contrast, lineages with unrestored apicobasal polarity maintained SOX9 activity in sustained efforts to regenerate, which were identified as a SOX9on-on Cadherin6pos cell state. These reprogrammed cells generated substantial single-cell WNT activity to provoke a fibroproliferative response in adjacent fibroblasts, driving AKI to chronic kidney disease. Transplanted human kidneys displayed similar SOX9/CDH6/WNT2B responses. Thus, we have uncovered a sensor of epithelial repair status, the activity of which determines regeneration with or without fibrosis.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Insuficiência Renal Crônica / Fatores de Transcrição SOX9 / Injúria Renal Aguda / Rim / Túbulos Renais Proximais Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Insuficiência Renal Crônica / Fatores de Transcrição SOX9 / Injúria Renal Aguda / Rim / Túbulos Renais Proximais Limite: Animals / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article