37
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Podocytes

      review-article
      a , 1 , 1
      F1000Research
      F1000Research
      Podocytes, kidney glomerulus, urinary ultrafiltrate, glomerular filtration

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Podocytes are highly specialized cells of the kidney glomerulus that wrap around capillaries and that neighbor cells of the Bowman’s capsule. When it comes to glomerular filtration, podocytes play an active role in preventing plasma proteins from entering the urinary ultrafiltrate by providing a barrier comprising filtration slits between foot processes, which in aggregate represent a dynamic network of cellular extensions. Foot processes interdigitate with foot processes from adjacent podocytes and form a network of narrow and rather uniform gaps. The fenestrated endothelial cells retain blood cells but permit passage of small solutes and an overlying basement membrane less permeable to macromolecules, in particular to albumin. The cytoskeletal dynamics and structural plasticity of podocytes as well as the signaling between each of these distinct layers are essential for an efficient glomerular filtration and thus for proper renal function. The genetic or acquired impairment of podocytes may lead to foot process effacement (podocyte fusion or retraction), a morphological hallmark of proteinuric renal diseases. Here, we briefly discuss aspects of a contemporary view of podocytes in glomerular filtration, the patterns of structural changes in podocytes associated with common glomerular diseases, and the current state of basic and clinical research.

          Related collections

          Most cited references324

          • Record: found
          • Abstract: found
          • Article: not found

          Overview of Complement Activation and Regulation

          Summary Complement is an important component of the innate immune system that is crucial for defense from microbial infections and for clearance of immune complexes and injured cells. In normal conditions complement is tightly controlled by a number of fluid-phase and cell surface proteins to avoid injury to autologous tissues. When complement is hyperactivated, as occurs in autoimmune diseases or in subjects with dysfunctional regulatory proteins, it drives a severe inflammatory response in numerous organs. The kidney appears to be particularly vulnerable to complement-mediated inflammatory injury. Injury may derive from deposition of circulating active complement fragments in glomeruli, but complement locally produced and activated in the kidney also may have a role. Many kidney disorders have been linked to abnormal complement activation, including immune-complex–mediated glomerulonephritis and rare genetic kidney diseases, but also tubulointerstitial injury associated with progressive proteinuric diseases or ischemia-reperfusion.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome.

            Familial idiopathic nephrotic syndromes represent a heterogeneous group of kidney disorders, and include autosomal recessive steroid-resistant nephrotic syndrome, which is characterized by early childhood onset of proteinuria, rapid progression to end-stage renal disease and focal segmental glomerulosclerosis. A causative gene for this disease, NPHS2, was mapped to 1q25-31 and we report here its identification by positional cloning. NPHS2 is almost exclusively expressed in the podocytes of fetal and mature kidney glomeruli, and encodes a new integral membrane protein, podocin, belonging to the stomatin protein family. We found ten different NPHS2 mutations, comprising nonsense, frameshift and missense mutations, to segregate with the disease, demonstrating a crucial role for podocin in the function of the glomerular filtration barrier.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases.

              Kidney disease affects over 20 million people in the United States alone. Although the causes of renal failure are diverse, the glomerular filtration barrier is often the target of injury. Dysregulation of VEGF expression within the glomerulus has been demonstrated in a wide range of primary and acquired renal diseases, although the significance of these changes is unknown. In the glomerulus, VEGF-A is highly expressed in podocytes that make up a major portion of the barrier between the blood and urinary spaces. In this paper, we show that glomerular-selective deletion or overexpression of VEGF-A leads to glomerular disease in mice. Podocyte-specific heterozygosity for VEGF-A resulted in renal disease by 2.5 weeks of age, characterized by proteinuria and endotheliosis, the renal lesion seen in preeclampsia. Homozygous deletion of VEGF-A in glomeruli resulted in perinatal lethality. Mutant kidneys failed to develop a filtration barrier due to defects in endothelial cell migration, differentiation, and survival. In contrast, podocyte-specific overexpression of the VEGF-164 isoform led to a striking collapsing glomerulopathy, the lesion seen in HIV-associated nephropathy. Our data demonstrate that tight regulation of VEGF-A signaling is critical for establishment and maintenance of the glomerular filtration barrier and strongly supports a pivotal role for VEGF-A in renal disease.
                Bookmark

                Author and article information

                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000Research (London, UK )
                2046-1402
                28 January 2016
                2016
                : 5
                : F1000 Faculty Rev-114
                Affiliations
                [1 ]Department of Medicine, Rush University Medical Center, Chicago, IL, USA
                Author notes

                Competing interests: Jochen Reiser has pending and issued patents on novel strategies for kidney therapeutics and stands to gain royalties from their commercialization. He is co-founder of TRISAQ (Miami, FL, USA), a biotechnology company in which he has financial interest, including stock. MA declares that he has no competing interests.

                Article
                10.12688/f1000research.7255.1
                4755401
                26918173
                ca9e67e5-2cf0-4dd6-a359-0afe5d276777
                Copyright: © 2016 Reiser J and Altintas MM

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 January 2016
                Funding
                The author(s) declared that no grants were involved in supporting this work.
                Categories
                Review
                Articles
                Animal Genetics
                Biocatalysis
                Cell Adhesion
                Cell Signaling
                Cellular Death & Stress Responses
                Cytoskeleton
                HIV Infection & AIDS: Clinical
                Immunopharmacology & Hematologic Pharmacology
                Medical Genetics
                Membranes & Sorting
                Protein Chemistry & Proteomics
                Renal Function & Transport Physiology
                Renal Immunology & Pathology (incl. Glomerular Diseases)
                Renal Pharmacology

                podocytes,kidney glomerulus,urinary ultrafiltrate,glomerular filtration

                Comments

                Comment on this article