Bone Marrow–Derived Progenitor Cells Do Not Contribute to Podocyte Turnover in the Puromycin Aminoglycoside and Renal Ablation Models in Rats

Meyer-Schwesinger, Catherine; Lange, Claudia; Bröcker, Verena; Agustian, Putri A.; Lehmann, Ulrich; Raabe, Annette; Brinkmeyer, Martina; Kobayashi, Eiji; Schiffer, Mario; Büsche, Guntram; Kreipe, Hans; Thaiss, Friedrich; Becker, Jan U.

doi:10.1016/j.ajpath.2010.10.024

Cited by 22 publications

(13 citation statements)

References 38 publications

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“…101 Although bone marrow-derived cells have been postulated to give rise to podocytes, 102 lineage tracing studies indicate that these cells likely do not contribute substantially to podocyte regeneration. 103 …”

Section: Pathophysiological Mechanismsmentioning

confidence: 99%

Causes and pathogenesis of focal segmental glomerulosclerosis

2014

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Focal segmental glomerulosclerosis (FSGS) describes both a common lesion in progressive kidney disease, and a disease characterized by marked proteinuria and podocyte injury. The initial injuries vary widely. Monogenetic forms of FSGS are largely due to alterations in structural genes of the podocyte, many of which result in early onset of disease. Genetic risk alleles in apolipoprotein L1 are especially prevalent in African Americans, and are linked not only to adult-onset FSGS but also to progression of some other kidney diseases. The recurrence of FSGS in some transplant recipients whose end-stage renal disease was caused by FSGS points to circulating factors in disease pathogenesis, which remain incompletely understood. In addition, infection, drug use, and secondary maladaptive responses after loss of nephrons from any cause may also cause FSGS. Varying phenotypes of the sclerosis are also manifest, with varying prognosis. The so-called tip lesion has the best prognosis, whereas the collapsing type of FSGS has the worst prognosis. New insights into glomerular cell injury response and repair may pave the way for possible therapeutic strategies.

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Section: Pathophysiological Mechanismsmentioning

confidence: 99%

Causes and pathogenesis of focal segmental glomerulosclerosis

2014

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“…38 Bone marrow derived stem cells are not podocyte progenitors in two experimental models. 39 Some studies in humans have suggested that PECs may serve this podocyte progenitor role and repopulate the glomerulus following podocyte loss 38,39 , although this remains controversial, as similar paradigms do not exist in adult mice. 40 (see below).…”

Section: Podocyte Depletion Is Required For the Development Of Classimentioning

confidence: 99%

The Pathogenesis of Focal Segmental Glomerulosclerosis

Jefferson

Shankland

2014

Advances in Chronic Kidney Disease

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Focal segmental glomerulosclerosis (FSGS) is a histological pattern of injury on renal biopsy that can arise from a diverse range of causes and mechanisms. Although primary and secondary forms are described based on the underlying cause, there are many common factors that underlie the development of this segmental injury. In this review we will describe the currently accepted model for the pathogenesis of classic FSGS and review the data supporting this model. Although the podocyte is considered the major target of injury in FSGS, we will also highlight the contributions of other resident glomerular cells in the development of FSGS.

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“…PAN was induced in Sprague-Dawley rats by intraperitoneal injection of puromycin aminonucleoside in PBS (Sigma-Aldrich) as described. 52 Puromycin aminonucleoside induces severe proteinuria and glomerular ultrastructural changes in rats by direct injury of the podocyte cytoskeleton, 53 leading to sustained foot-process effacement, podocyte loss, glomerular sclerosis, and proteinuria resembling human FSGS. Animals were euthanized on day 14, 18, 28, 35 (PHN), or 28 (PAN) for additional analyses when persistent injury with morphologic changes, such as focal sclerosis in PAN and podocyte swelling and loss in PHN, was established.…”

Section: Animal Experimentsmentioning

confidence: 99%

Alterations in the Ubiquitin Proteasome System in Persistent but Not Reversible Proteinuric Diseases

Beeken¹,

Lindenmeyer

Blattner

et al. 2014

Journal of the American Society of Nephrology

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Podocytes are the key cells affected in nephrotic glomerular kidney diseases, and they respond uniformly to injury with cytoskeletal rearrangement. In nephrotic diseases, such as membranous nephropathy and FSGS, persistent injury often leads to irreversible structural damage, whereas in minimal change disease, structural alterations are mostly transient. The factors leading to persistent podocyte injury are currently unknown. Proteolysis is an irreversible process and could trigger persistent podocyte injury through degradation of podocyte-specific proteins. We, therefore, analyzed the expression and functional consequence of the two most prominent proteolytic systems, the ubiquitin proteasome system (UPS) and the autophagosomal/lysosomal system, in persistent and transient podocyte injuries. We show that differential upregulation of both proteolytic systems occurs in persistent human and rodent podocyte injury. The expression of specific UPS proteins in podocytes differentiated children with minimal change disease from children with FSGS and correlated with poor clinical outcome. Degradation of the podocytespecific protein a-actinin-4 by the UPS depended on oxidative modification in membranous nephropathy. Notably, the UPS was overwhelmed in podocytes during experimental glomerular disease, resulting in abnormal protein accumulation and compensatory upregulation of the autophagosomal/lysosomal system. Accordingly, inhibition of both proteolytic systems enhanced proteinuria in persistent nephrotic disease. This study identifies altered proteolysis as a feature of persistent podocyte injury. In the future, specific UPS proteins may serve as new biomarkers or therapeutic targets in persistent nephrotic syndrome.

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Bone Marrow–Derived Progenitor Cells Do Not Contribute to Podocyte Turnover in the Puromycin Aminoglycoside and Renal Ablation Models in Rats

Cited by 22 publications

References 38 publications

Causes and pathogenesis of focal segmental glomerulosclerosis

Causes and pathogenesis of focal segmental glomerulosclerosis

The Pathogenesis of Focal Segmental Glomerulosclerosis

Alterations in the Ubiquitin Proteasome System in Persistent but Not Reversible Proteinuric Diseases

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