title: Dendrin ablation prolongs life span by delaying kidney failure.
abstract: Podocyte loss is central to the progression of proteinuric kidney diseases leading to end-stage kidney disease (ESKD), requiring renal replacement therapy, such as dialysis. Despite modern tools and techniques, the 5-year mortality of some patients requiring dialysis remains at about 70% to 80%. Thus, there is a great unmet need for podocyte-specific treatments aimed at preventing podocyte loss and the ensuing development of ESKD. Here, we show that ablation of the podocyte death-promoting protein dendrin delays the onset of ESKD, thereby expanding the life span of mice lacking the adapter protein CD2AP. Ablation of dendrin delays onset and severity of proteinuria and podocyte loss. In addition, dendrin ablation ameliorates mesangial volume expansion and up-regulation of mesangial fibronectin expression, which is mediated by a podocyte-secreted factor. In conclusion, onset of ESKD and death can be markedly delayed by blocking the function of dendrin.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Astrid
authors.initials: A
authors.lastname: Weins
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Jenny S
authors.initials: JS
authors.lastname: Wong
authors.affiliation: Department of Research, Morphometry and Stereology Laboratory, Charles R. Drew University of Medicine and Science, Los Angeles, California.
authors.forename: John M
authors.initials: JM
authors.lastname: Basgen
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Medicine, Bronx, New York.
authors.forename: Ritu
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Ilse
authors.initials: I
authors.lastname: Daehn
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Lisette
authors.initials: L
authors.lastname: Casagrande
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: David
authors.initials: D
authors.lastname: Lessman
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Monica
authors.initials: M
authors.lastname: Schwartzman
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Kristin
authors.initials: K
authors.lastname: Meliambro
authors.affiliation: KI/AZ Integrated CardioMetabolic Center (ICMC), Department of Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Jaakko
authors.initials: J
authors.lastname: Patrakka
authors.affiliation: Division of Immunobiology, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Andrey
authors.initials: A
authors.lastname: Shaw
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: John Cijiang
authors.initials: JC
authors.lastname: He
authors.affiliation: Division of Nephrology, University of California Los Angeles, Los Angeles, California.
authors.forename: Susanne B
authors.initials: SB
authors.lastname: Nicholas
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Peter
authors.initials: P
authors.lastname: Mundel
authors.affiliation: Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: kirk.campbell@mssm.edu.
authors.forename: Kirk N
authors.initials: KN
authors.lastname: Campbell
mesh_terms: D000818:Animals; D018450:Disease Progression; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008136:Longevity / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism / Q000473:pathology*; D011507:Proteinuria / Q000378:metabolism / Q000473:pathology
chemical_list: D009419:Nerve Tissue Proteins; C104328:dendrin