scholarly journals Cre recombinase toxicity in podocytes: a novel genetic model for FSGS in adolescent mice

2019 ◽  
Vol 317 (5) ◽  
pp. F1375-F1382 ◽  
Author(s):  
Madeleine Frahsek ◽  
Kevin Schulte ◽  
Arnaldo Chia-Gil ◽  
Sonja Djudjaj ◽  
Herdit Schueler ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Focal Segmental Glomerulosclerosis ◽  
Genetic Model ◽  
Transgenic Animals ◽  
Cre Recombinase ◽  
Young Age ◽  
Podocyte Injury ◽  
Sclerotic Lesions ◽  
Parietal Epithelial Cells ◽  
Time Point

Here, we show that inducible overexpression of Cre recombinase in glomerular podocytes but not in parietal epithelial cells may trigger focal segmental glomerulosclerosis (FSGS) in juvenile transgenic homocygous Pod-rtTA/LC1 mice. Administration of doxycycline shortly after birth, but not at any other time point later in life, resulted in podocyte injury and development of classical FSGS lesions in these mice. Sclerotic lesions were formed as soon as 3 wk of age, and FSGS progressed with low variability until 13 wk of age. In addition, our experiments identified Cre toxicity as a potentially relevant limitation for studies in podocytes of transgenic animals. In summary, our study establishes a novel genetic model for FSGS in mice, which exhibits low variability and manifests already at a young age.

scholarly journals Parietal epithelial cells maintain the epithelial cell continuum forming Bowman's space in focal segmental glomerulosclerosis

2021 ◽  
Author(s):  
Laura Miesen ◽  
Péter Bándi ◽  
Brigith Willemsen ◽  
Fieke Mooren ◽  
Thiago Strieder ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Focal Segmental Glomerulosclerosis ◽  
Glomerular Epithelial Cell ◽  
Segmental Glomerulosclerosis ◽  
Glomerular Epithelial Cells ◽  
Tubular System ◽  
Sclerotic Lesions ◽  
Parietal Epithelial Cells ◽  
Glomerular Tuft

In the glomerulus, Bowman's space is formed by a continuum of glomerular epithelial cells. In focal segmental glomerulosclerosis (FSGS), glomeruli show segmental scarring, a result of activated PECs invading the glomerular tuft. The segmental scars interrupt the epithelial continuum. However, non-sclerotic segments seem to be preserved even in glomeruli with advanced lesions. We studied the histology of the segmental pattern in Munich Wistar Frömter (MWF) rats, a model for secondary FSGS. Our results showed that matrix layers lined with PECs cover the sclerotic lesions. These PECs formed contacts with podocytes of the uninvolved tuft segments, restoring the epithelial continuum. Formed Bowman's spaces were still connected to the tubular system. Furthermore, in biopsies of patients with secondary FSGS we also detected matrix layers formed by PECs, separating the uninvolved from the sclerotic glomerular segments. While PECs have a major role in the formation of glomerulosclerosis, we showed that in FSGS, PECs also restore the glomerular epithelial cell continuum that surrounds Bowman's space. This process may be beneficial and indispensable for glomerular filtration in the uninvolved segments of sclerotic glomeruli.

scholarly journals Mechanisms of Scarring in Focal Segmental Glomerulosclerosis

2021 ◽  
pp. 1-9
Author(s):  
Ke Sun ◽  
Qionghong Xie ◽  
Chuan-Ming Hao
Keyword(s):  
Epithelial Cells ◽  
Influencing Factors ◽  
Focal Segmental Glomerulosclerosis ◽  
Therapeutic Strategies ◽  
Podocyte Injury ◽  
Segmental Glomerulosclerosis ◽  
Potential Sources ◽  
Histologic Pattern ◽  
Parietal Epithelial Cells

<b><i>Background:</i></b> Focal segmental glomerulosclerosis (FSGS) is a histologic pattern characterized by focal glomerular scarring, which often progresses to systemic and diffuse glomerulosclerosis. Previous studies have emphasized that the initiation of classic FSGS occurs in podocytes. The dysfunction and loss of podocytes have been associated with the development of proteinuria and the progression of various diseases. In addition, primary, secondary, and genetic FSGS are caused by different mechanisms of podocyte injury. <b><i>Summary:</i></b> The potential sources and mechanism of podocyte supplementation are the focus of our current research. Increasing attention has been paid to the role played by parietal epithelial cells (PECs) during the progression of FSGS. PECs are not only the primary influencing factors in glomerulosclerosis lesions but also have repair abilities, which remain a focus of debate. Notably, other resident glomerular cells also play significant roles in the progression of this disease. <b><i>Key Message:</i></b> In this review, we focus on the mechanism of scarring in FSGS and discuss current and potential therapeutic strategies.

scholarly journals Mechanisms of Scarring in Focal Segmental Glomerulosclerosis

2019 ◽  
Vol 67 (9) ◽  
pp. 623-632
Author(s):  
Jianyong Zhong ◽  
Jacob B. Whitman ◽  
Hai-Chun Yang ◽  
Agnes B. Fogo
Keyword(s):  
Epithelial Cells ◽  
Focal Segmental Glomerulosclerosis ◽  
Genetic Mutation ◽  
Tubular Epithelial Cells ◽  
Podocyte Injury ◽  
Segmental Glomerulosclerosis ◽  
Initial Injury ◽  
Parietal Epithelial Cells ◽  
Initial Target ◽  
Increased Susceptibility

Focal segmental glomerulosclerosis (FSGS) presents with scar in parts of some glomeruli and often progresses to global and diffuse glomerulosclerosis. Podocyte injury is the initial target in primary FSGS, induced by a circulating factor. Several gene variants, for example, APOL1, are associated with increased susceptibility to FSGS. Primary FSGS may be due to genetic mutation in key podocyte genes. Increased work stress after loss of nephrons, epigenetic mechanisms, and various profibrotic pathways can contribute to progressive sclerosis, regardless of the initial injury. The progression of FSGS lesions also involves crosstalk between podocytes and other kidney cells, such as parietal epithelial cells, glomerular endothelial cells, and even tubular epithelial cells. New insights related to these mechanisms could potentially lead to new therapeutic strategies to prevent progression of FSGS.

scholarly journals Podocyte Injury in Lupus Nephritis

2019 ◽  
Vol 8 (9) ◽  
pp. 1340 ◽  
Author(s):  
Hamza Sakhi ◽  
Anissa Moktefi ◽  
Khedidja Bouachi ◽  
Vincent Audard ◽  
Carole Hénique ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Glomerular Injury ◽  
Crescent Formation ◽  
Podocyte Injury ◽  
Inflammatory Processes ◽  
Lupus Podocytopathy ◽  
Parietal Epithelial Cells ◽  
Lupus Glomerulonephritis

Systemic lupus erythematosus (SLE) is characterized by a broad spectrum of renal lesions. In lupus glomerulonephritis, histological classifications are based on immune-complex (IC) deposits and hypercellularity lesions (mesangial and/or endocapillary) in the glomeruli. However, there is compelling evidence to suggest that glomerular epithelial cells, and podocytes in particular, are also involved in glomerular injury in patients with SLE. Podocytes now appear to be not only subject to collateral damage due to glomerular capillary lesions secondary to IC and inflammatory processes, but they are also a potential direct target in lupus nephritis. Improvements in our understanding of podocyte injury could improve the classification of lupus glomerulonephritis. Indeed, podocyte injury may be prominent in two major presentations: lupus podocytopathy and glomerular crescent formation, in which glomerular parietal epithelial cells play also a key role. We review here the contribution of podocyte impairment to different presentations of lupus nephritis, focusing on the podocyte signaling pathways involved in these lesions.

Up-Regulation of CD74 Expression in Parietal Epithelial Cells in a Mouse Model of Focal Segmental Glomerulosclerosis

Nephron ◽  
2016 ◽  
Vol 134 (4) ◽  
pp. 238-252 ◽  
Author(s):  
Takeshi Yamazaki ◽  
Satoshi Sasaki ◽  
Takayuki Okamoto ◽  
Yasuyuki Sato ◽  
Asako Hayashi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Focal Segmental Glomerulosclerosis ◽  
Segmental Glomerulosclerosis ◽  
Parietal Epithelial Cells

Is CD44 in glomerular parietal epithelial cells a pathological marker of renal function deterioration in primary focal segmental glomerulosclerosis?

2017 ◽  
Vol 32 (11) ◽  
pp. 2165-2169 ◽  
Author(s):  
Brunna Pinto Froes ◽  
Stanley de Almeida Araújo ◽  
Eduardo Alves Bambirra ◽  
Eduardo Araújo Oliveira ◽  
Ana Cristina Simões e Silva ◽  
...  
Keyword(s):  
Renal Function ◽  
Epithelial Cells ◽  
Focal Segmental Glomerulosclerosis ◽  
Segmental Glomerulosclerosis ◽  
Renal Function Deterioration ◽  
Parietal Epithelial Cells

scholarly journals Glomerular parietal epithelial cells contribute to adult podocyte regeneration in experimental focal segmental glomerulosclerosis

2015 ◽  
Vol 88 (5) ◽  
pp. 999-1012 ◽  
Author(s):  
Diana G. Eng ◽  
Maria W. Sunseri ◽  
Natalya V. Kaverina ◽  
Sebastian S. Roeder ◽  
Jeffrey W. Pippin ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Focal Segmental Glomerulosclerosis ◽  
Segmental Glomerulosclerosis ◽  
Parietal Epithelial Cells ◽  
Podocyte Regeneration

scholarly journals Potential role of Claudin-1 immunohistochemical expression and ultrastructural changes in detecting early focal segmental glomerulosclerosis

2019 ◽  
Vol 8 (3) ◽  
pp. 24-24
Author(s):  
Nadia Galal Elhefnawy ◽  
Nermine Mohamed Adb Raboh ◽  
Ola Hassan Nada ◽  
Esraa Adel Mahmoud ◽  
Waleed Anwar Abd El Mohsen
Keyword(s):  
Nephrotic Syndrome ◽  
Focal Segmental Glomerulosclerosis ◽  
Ultrastructural Changes ◽  
Segmental Glomerulosclerosis ◽  
Disease Entities ◽  
Sclerotic Lesions ◽  
Stage Renal Disease ◽  
End Stage ◽  
Parietal Epithelial Cells

Background: Focal segmental glomerulosclerosis (FSGS) and Minimal change disease (MCD) are two disease entities presented mainly by nephrotic syndrome. While 95% of MCD cases showed complete remission on steroid therapy, 50% of FSGS cases progress to end stage renal disease. Early sclerotic lesions in FSGS can be missed in routine H&E examination. Objective: To differentiate early FSGS from MCD by detection of activated parietal epithelial cells (PECs) in early glomerular sclerotic lesions using Claudin-1 immunohistochemical (IHC) staining and by examining podocyte ultrastructural changes. Materials and Methods: This retrospective study included 28 cases diagnosed as MCD and 20 cases diagnosed as early FSGS. Clinicopathologic data collection, claudin-1 IHC staining and reviewing ultrastructural changes were performed and the results were statistically analyzed. Results: A statistically significant correlation was detected between claudin-1 expression and the initial diagnosis of the studied groups (P=0.005). Claudin-1 was expressed in a visceral location in (39.28%) of the biopsies initially diagnosed as MCD thus were reevaluated as early FSGS lesions. 63.64% of these positive cases were presented by steroid resistant nephrotic syndrome and 63.6% of which showed some ultrastructural changes of FSGS in podocytes including abnormalities in mitochondrial shapes, endoplasmic reticulum changes and a decreased number of autophagic vacuoles. Conclusion: Claudin-1 is a novel diagnostic marker that can differentiate between confusing cases of early FSGS versus MCD. Defective autophagy plays a role in the pathogenesis of FSGS.

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