ffbf25ec3b82bde7e85228bd6b522da4 pmc_35163470.pdf 0143d97b651531f507008c4321d5fb57ad392083 pmc_35163470.pdf 13c8d52baf0968983bee88dbe8a0a8adfc52f220337bc709345f8071941c57d8 pmc_35163470.pdf Title: Molecular Mechanisms of Kidney Injury and Repair Subject: Chronic kidney disease (CKD) will become the fifth global cause of death by 2040, thus emphasizing the need to better understand the molecular mechanisms of damage and regeneration in the kidney. CKD predisposes to acute kidney injury (AKI) which, in turn, promotes CKD progression. This implies that CKD or the AKI-to-CKD transition are associated with dysfunctional kidney repair mechanisms. Current therapeutic options slow CKD progression but fail to treat or accelerate recovery from AKI and are unable to promote kidney regeneration. Unraveling the cellular and molecular mechanisms involved in kidney injury and repair, including the failure of this process, may provide novel biomarkers and therapeutic tools. We now review the contribution of different molecular and cellular events to the AKI-to-CKD transition, focusing on the role of macrophages in kidney injury, the different forms of regulated cell death and necroinflammation, cellular senescence and the senescence-associated secretory phenotype (SAPS), polyploidization, and podocyte injury and activation of parietal epithelial cells. Next, we discuss key contributors to repair of kidney injury and opportunities for their therapeutic manipulation, with a focus on resident renal progenitor cells, stem cells and their reparative secretome, certain macrophage subphenotypes within the M2 phenotype and senescent cell clearance. Keywords: acute kidney injury; chronic kidney disease; regeneration; kidney; molecular mechanisms; cell death; treatment Author: Sandra Rayego-Mateos, Laura Marquez-Expósito, Raquel Rodrigues-Diez, Ana B. Sanz, Roser Guiteras, Nuria Doladé, Irene Rubio-Soto, Anna Manonelles, Sergi Codina, Alberto Ortiz, Josep M. Cruzado, Marta Ruiz-Ortega and Anna Sola Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Feb 3 10:57:51 2022 CET ModDate: Thu Feb 3 11:02:49 2022 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 20 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2697121 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- EUNBMT+VnURWPalladioL Type 1 Custom yes yes no 10 0 UYPFSM+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 BMCNBX+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 IZBDLK+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 HJOMHV+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 36 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 40 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 44 0 IRWHZX+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 56 0 CKUPDE+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 59 0 LHCXDL+EURM10 Type 1 Builtin yes yes no 87 0 CRUZTT+VnURWPalladioL-Italic Type 1 Custom yes yes no 128 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-05-07 04:29:39 CEST RepresentationInformation: pmc_35163470.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2022-02-27 18:40:42 CET Size: 2697121 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 749 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Molecular and Cellular Events Contributing to the AKI-to-CKD Transition Destination: section.2 Children: Item: Title: Macrophages in Kidney Injury Destination: subsection.2.1 Item: Title: Regulated Cell Death Destination: subsection.2.2 Item: Title: Cellular Senescence Destination: subsection.2.3 Item: Title: The Senescence-Associated Secretory Phenotype (SAPS) Destination: subsection.2.4 Item: Title: Polyploidization: A Question of Size; Samson or Delilah Destination: subsection.2.5 Item: Title: Podocyte Damage and Activation of Parietal Epithelial Cells Destination: subsection.2.6 Item: Title: Recovery and Repair Strategies Destination: section.3 Children: Item: Title: Resident Renal Progenitor Cells Destination: subsection.3.1 Item: Title: Stem Cells and the Reparative Secretome Destination: subsection.3.2 Item: Title: Macrophages in Repair Destination: subsection.3.3 Item: Title: Senescent Cell Clearance: Senotherapies Destination: subsection.3.4 Item: Title: AKI/CKD-to-Cancer Transition Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Molecular Mechanisms of Kidney Injury and Repair Author: Sandra Rayego-Mateos, Laura Marquez-Expósito, Raquel Rodrigues-Diez, Ana B. Sanz, Roser Guiteras, Nuria Doladé, Irene Rubio-Soto, Anna Manonelles, Sergi Codina, Alberto Ortiz, Josep M. Cruzado, Marta Ruiz-Ortega and Anna Sola Subject: Chronic kidney disease (CKD) will become the fifth global cause of death by 2040, thus emphasizing the need to better understand the molecular mechanisms of damage and regeneration in the kidney. CKD predisposes to acute kidney injury (AKI) which, in turn, promotes CKD progression. This implies that CKD or the AKI-to-CKD transition are associated with dysfunctional kidney repair mechanisms. Current therapeutic options slow CKD progression but fail to treat or accelerate recovery from AKI and are unable to promote kidney regeneration. Unraveling the cellular and molecular mechanisms involved in kidney injury and repair, including the failure of this process, may provide novel biomarkers and therapeutic tools. We now review the contribution of different molecular and cellular events to the AKI-to-CKD transition, focusing on the role of macrophages in kidney injury, the different forms of regulated cell death and necroinflammation, cellular senescence and the senescence-associated secretory phenotype (SAPS), polyploidization, and podocyte injury and activation of parietal epithelial cells. Next, we discuss key contributors to repair of kidney injury and opportunities for their therapeutic manipulation, with a focus on resident renal progenitor cells, stem cells and their reparative secretome, certain macrophage subphenotypes within the M2 phenotype and senescent cell clearance. Keywords: acute kidney injury; chronic kidney disease; regeneration; kidney; molecular mechanisms; cell death; treatment Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Feb 03 10:57:51 CET 2022 ModDate: Thu Feb 03 11:02:49 CET 2022 ID: 0x1aaa1a42b07050502befc9ca73125dd8, 0x1aaa1a42b07050502befc9ca73125dd8 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: CRUZTT+VnURWPalladioL-Italic FontSubset: true FirstChar: 189 LastChar: 189 FontDescriptor: FontName: CRUZTT+VnURWPalladioL-Italic Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: BMCNBX+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: BMCNBX+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: LHCXDL+EURM10 FontSubset: true FirstChar: 11 LastChar: 20 FontDescriptor: FontName: LHCXDL+EURM10 Flags: Symbolic 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