Primary proximal tubule injury leads to epithelial cell cycle arrest, fibrosis, vascular rarefaction, and glomerulosclerosis  Joseph V. Bonventre  Kidney.

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Primary proximal tubule injury leads to epithelial cell cycle arrest, fibrosis, vascular rarefaction, and glomerulosclerosis  Joseph V. Bonventre  Kidney International Supplements  Volume 4, Issue 1, Pages 39-44 (November 2014) DOI: 10.1038/kisup.2014.8 Copyright © 2014 International Society of Nephrology Terms and Conditions

Figure 1 Adaptive and maladaptive repair after injury. After mild injury self-limited over time and to a kidney that has not sustained prior insults of significance, damaged proximal tubule cells are replaced by surviving proximal tubule cells that dedifferentiate, proliferate, and restore the normal epithelium. By contrast, if the injury is more severe, repeated, or to a kidney that is abnormal at baseline, then the cells that are stimulated to proliferate cannot complete the cell cycle efficiently and often are arrested in G2/M. Apoptosis of these cells may be blocked so that they continue to survive. They then turn on signaling pathways involving Jun N-terminal kinase (JNK), and activate pro-fibrotic gene transcription. This sets off a sequence of events resulting in vascular rarefaction, myofibroblast proliferation, and deposition of collagens and other matrix components in the interstitium. Kidney International Supplements 2014 4, 39-44DOI: (10.1038/kisup.2014.8) Copyright © 2014 International Society of Nephrology Terms and Conditions

Figure 2 In vivo cell cycle analysis in acute kidney injury (AKI). Proximal tubule cell cycle distribution (G1, S, and G2/M) of cells in the cell cycle over 42 days after moderate ischemia reperfusion injury (IRI; top left), unilateral ischemia/reperfusion (bottom left), and after administration of aristolochic acid (bottom right; n=3 mice of each time point in each group). AAN, aristolochic acid nephropathy. (Modified from Yang et al.14) Kidney International Supplements 2014 4, 39-44DOI: (10.1038/kisup.2014.8) Copyright © 2014 International Society of Nephrology Terms and Conditions