title: New insights into the pathology of podocyte loss: mitotic catastrophe.
abstract: Podocytes represent an essential component of the kidney's glomerular filtration barrier. They stay attached to the glomerular basement membrane via integrin interactions that support the capillary wall to withstand the pulsating filtration pressure. Podocyte structure is maintained by a dynamic actin cytoskeleton. Terminal differentiation is coupled with permanent exit from the cell cycle and arrest in a postmitotic state. Postmitotic podocytes do not have an infinite life span; in fact, physiologic loss in the urine is documented. Proteinuria and other injuries accelerate podocyte loss or induce death. Mature podocytes are unable to replicate and maintain their actin cytoskeleton simultaneously. By the end of mitosis, cytoskeletal actin forms part of the contractile ring, rendering a round shape to podocytes. Therefore, when podocyte mitosis is attempted, it may lead to aberrant mitosis (ie, mitotic catastrophe). Mitotic catastrophe implies that mitotic podocytes eventually detach or die; this is a previously unrecognized form of podocyte loss and a compensatory mechanism for podocyte hypertrophy that relies on post-G1-phase cell cycle arrest. In contrast, local podocyte progenitors (parietal epithelial cells) exhibit a simple actin cytoskeleton structure and can easily undergo mitosis, supporting podocyte regeneration. In this review we provide an appraisal of the in situ pathology of mitotic catastrophe compared with other proposed types of podocyte death and put experimental and renal biopsy data in a unified perspective.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri; Department of Internal Medicine (Renal), Washington University School of Medicine, St. Louis, Missouri. Electronic address: liapis@path.wustl.edu.
authors.forename: Helen
authors.initials: H
authors.lastname: Liapis
authors.affiliation: Excellence Centre for Research, Transfer and High Education for the Development of de Novo Therapies (DENOTHE), Florence, Italy; Pediatric Nephrology Unit, Meyer Children's Hospital, Florence, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Romagnani
authors.affiliation: Nephrology Center, Medical Hospital and Health Center IV, University of Munich Clinical Center-LMU, Campus Innenstadt, Munich, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
mesh_terms: D000818:Animals; D016923:Cell Death; D015658:HIV Infections / Q000150:complications / Q000473:pathology; D006801:Humans; D006984:Hypertrophy; D007674:Kidney Diseases / Q000150:complications / Q000473:pathology / Q000821:virology; D008938:Mitosis; D050199:Podocytes / Q000473:pathology* / Q000648:ultrastructure