scholarly journals Castrated autoimmune glomerulonephritis mouse model shows attenuated glomerular sclerosis with altered parietal epithelial cell phenotype

2021 ◽  
pp. 153537022199601
Author(s):  
Yuki Otani ◽  
Osamu Ichii ◽  
Md. Abdul Masum ◽  
Takashi Namba ◽  
Teppei Nakamura ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Sex Hormones ◽  
Cell Number ◽  
Glomerular Sclerosis ◽  
Cell Phenotype ◽  
Autoantibody Production ◽  
Parietal Epithelial Cell ◽  
Parietal Epithelial Cells

Sex hormones help in maintaining proper immunity as well as renal homeostasis in mammals, and these multi-functional properties characterize the onset of sex-dependent diseases. To clarify the contribution of sex hormones to autoimmune disease-related renal pathogenesis, BXSB/MpJ- Yaa was investigated as a murine autoimmune glomerulonephritis model. BXSB/MpJ- Yaa and its wild-type, BXSB/MpJ- Yaa+ were castrated or sham-operated at three weeks and examined until six months of age. Both castrated strains showed significantly lower serum testosterone levels and body weights than sham-operated mice. Castration did not change the disease phenotypes in BXSB/MpJ- Yaa+. At three months, both sham-operated and castrated BXSB/MpJ- Yaa manifested splenomegaly, autoantibody production, and glomerulonephritis, and castrated BXSB/MpJ- Yaa tended to show heavier spleen weights than the sham-operated group. At six months, both the treated BXSB/MpJ- Yaa showed equivalent autoimmune disease conditions; however, castrated mice clearly showed milder glomerular sclerotic lesions than the sham-operated groups. Urinary albumin excretion in castrated BXSB/MpJ- Yaa was significantly milder than in sham-operated mice at four months, but those of both the treated BXSB/MpJ- Yaa were comparable at six months. The examined renal histopathological indices in parietal epithelial cells were remarkably altered by castration. Briefly, castration decreased the height of parietal epithelial cells and total parietal epithelial cell number in BXSB/MpJ- Yaa at six months. For immunostaining, parietal epithelial cells facing the injured glomeruli of BXSB/MpJ- Yaa expressed CD44, an activated parietal epithelial cell marker, and CD44-positive parietal epithelial cells showed nuclear localization of the androgen receptor and proliferation marker Ki67. CD44- or Ki67-positive parietal epithelial cells were significantly fewer in castrated group than in sham-operated BXSB/MpJ- Yaa at six months. Further, quantitative indices for CD44-positive parietal epithelial cell number and frequency in renal corpuscles positively correlated with glomerular sclerotic severity in BXSB/MpJ- Yaa. In conclusion, androgen seemed to have an effect on both systemic immunity and renal morpho-function; however, the effect on the latter could be more clearly observed in BXSB/MpJ- Yaa, as parietal epithelial cell activation resulted in glomerular sclerosis.

scholarly journals c-Src inactivation reduces renal epithelial cell-matrix adhesion, proliferation, and cyst formation

2011 ◽  
Vol 301 (2) ◽  
pp. C522-C529 ◽  
Author(s):  
Justine Elliott ◽  
Nadezhda N. Zheleznova ◽  
Patricia D. Wilson
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Collecting Duct ◽  
Specific Inhibitor ◽  
Cell Phenotype ◽  
Epithelial Cell Proliferation ◽  
Matrix Adhesion ◽  
Cyst Lining

c-Src is a non-receptor tyrosine kinase whose activity is induced by phosphorylation at Y418 and translocation from the cytoplasm to the cell membrane. Increased activity of c-Src has been associated with cell proliferation, matrix adhesion, motility, and apoptosis in tumors. Immunohistochemistry suggested that activated (pY418)-Src activity is increased in cyst-lining autosomal dominant polycystic kidney disease (ADPKD) epithelial cells in human and mouse ADPKD. Western blot analysis showed that SKI-606 (Wyeth) is a specific inhibitor of pY418-Src without demonstrable effects on epidermal growth factor receptor or ErbB2 activity in renal epithelia. In vitro studies on mouse inner medullary collecting duct (mIMCD) cells and human ADPKD cyst-lining epithelial cells showed that SKI-606 inhibited epithelial cell proliferation over a 24-h time frame. In addition, SKI-606 treatment caused a striking statistically significant decrease in adhesion of mIMCD and human ADPKD to extracellular collagen matrix. Retained viability of unattached cells was consistent with a primary effect on epithelial cell anchorage dependence mediated by the loss of extracellular matrix (ECM)-attachment due to α2β1-integrin function. SKI-606-mediated attenuation of the human ADPKD hyperproliferative and hyper-ECM-adhesive epithelial cell phenotype in vitro was paralleled by retardation of the renal cystic phenotype of Pkd1 orthologous ADPKD heterozygous mice in vivo. This suggests that SKI-606 has dual effects on cystic epithelial cell proliferation and ECM adhesion and may have therapeutic potential for ADPKD patients.

scholarly journals Effect of Glutamine on Apoptosis-inducing Factor Expression and Apoptosis of Glomerular Parietal Epithelial Cells of Cisplatin-exposed Rats

2021 ◽  
Vol 9 (A) ◽  
pp. 367-372
Author(s):  
Ihsan Fahmi Rofananda ◽  
Jusak Nugraha ◽  
Imam Susilo ◽  
Miyayu Soneta Sofyan
Keyword(s):  
Epithelial Cells ◽  
Tissue Samples ◽  
Apoptosis Rate ◽  
Significant Difference ◽  
Parietal Epithelial Cell ◽  
Parietal Epithelial Cells ◽  
Apoptosis Inducing Factor ◽  
Post Hoc ◽  
Nephroprotective Effect ◽  
Test Result

AIM: This study analyzed the nephroprotective effect by examining apoptosis-inducing factor (AIF) expression and apoptosis rate in the glomerular parietal epithelial cell of cisplatin-exposed rats. METHODS: Samples consisted of 30 rats (divided into 3 groups: Group P0 received no treatment, group P1 received a cisplatin injection on the 7th day, and group P2 received glutamine injection on days 1–7 and cisplatin injection on the 7th day). After 72 h, the tissue samples were immunohistochemically processed. AIF expression was measured in an Allred score. The apoptosis rate was measured in apoptotic cells/field of view. Statistical analysis was carried out using JASP Statistics ver. 0.12.0 (p < 0.05). RESULTS: AIF expression values are follows: P0 = 4.89 ± 0.418, P1 = 6.14 ± 0.685, and P2 = 4.95 ± 0.530. The Kruskal–Wallis test result showed a significant difference (p < 0.05) between the groups and Dunn’s post hoc test showed a significant difference between P0 and P1 and between P1 and P2, but no significant difference between P0 and P2. Meanwhile, apoptosis rate values are as follows: P0 = 24.3 ± 9.821, P1 = 123.6 ± 16.008, and P2 = 77.2 ± 10.644. The Kruskal–Wallis test result showed a significant difference (p < 0.05) between the groups, and Dunn’s post hoc test showed a significant difference between P0 and P1, between P1 and P2, and between P0 and P2. CONCLUSION: The expression of AIF and apoptosis of glomerular parietal epithelial cells of the cisplatin-exposed rat has decreased after glutamine treatment.

scholarly journals New Insights into Glomerular Parietal Epithelial Cell Activation and Its Signaling Pathways in Glomerular Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Hua Su ◽  
Shan Chen ◽  
Fang-Fang He ◽  
Yu-Mei Wang ◽  
Philip Bondzie ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Signaling Pathways ◽  
Membranous Nephropathy ◽  
Cell Activation ◽  
Crescentic Glomerulonephritis ◽  
Diabetic Glomerulopathy ◽  
Glomerular Diseases ◽  
The Past ◽  
Parietal Epithelial Cell ◽  
Parietal Epithelial Cells

The glomerular parietal epithelial cells (PECs) have aroused an increasing attention recently. The proliferation of PECs is the main feature of crescentic glomerulonephritis; besides that, in the past decade, PEC activation has been identified in several types of noninflammatory glomerulonephropathies, such as focal segmental glomerulosclerosis, diabetic glomerulopathy, and membranous nephropathy. The pathogenesis of PEC activation is poorly understood; however, a few studies delicately elucidate the potential mechanisms and signaling pathways implicated in these processes. In this review we will focus on the latest observations and concepts about PEC activation in glomerular diseases and the newest identified signaling pathways in PEC activation.

scholarly journals Cells of NG2 lineage increase in glomeruli of mice following podocyte depletion

2018 ◽  
Vol 315 (5) ◽  
pp. F1449-F1464 ◽  
Author(s):  
Taihei Suzuki ◽  
Diana G. Eng ◽  
Aaron D. McClelland ◽  
Jeffrey W. Pippin ◽  
Stuart J. Shankland
Keyword(s):  
Epithelial Cell ◽  
Cell Types ◽  
Lineage Tracing ◽  
Cell Fates ◽  
Kinase Substrate ◽  
Parietal Epithelial Cell ◽  
Fluorescence Protein ◽  
Red Fluorescence Protein ◽  
Podocyte Proteins ◽  
Parietal Epithelial Cells

Under certain circumstances, podocytes can be partially replaced following their loss in disease. The inability of podocytes to proliferate suggests that replacement derives from other cell types. Because neural/glial antigen 2 (NG2)-expressing cells can serve as progenitors in other organs and because herein we showed increased NG2 staining in podocytes following their loss in experimental focal segmental glomerulosclerosis, we used lineage tracing in NG2-CreER tdTomato mice to test the hypothesis that partial podocyte replacement might derive from this cell population. The percentage of glomeruli with red fluorescence protein (RFP)-labeled NG2 cells increased following podocyte depletion, which was augmented by enalapril. However, BrdU was not detected in RFP-labeled cells, consistent with the migration of these cells to the glomerulus. Within glomeruli, RFP-labeled cells did not coexpress podocyte proteins (p57, synaptopodin, nephrin, or podocin) but did coexpress markers for mesangial (α8 integrin, PDGFβ receptor) and parietal epithelial cells (PAX8, src-suppressed C-kinase substrate). These results suggest that following podocyte depletion, cells of NG2 lineage do not serve as adult podocyte progenitors but have the ability to transdifferentiate to mesangial and parietal epithelial cell fates.

Role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells

2004 ◽  
Vol 286 (4) ◽  
pp. L650-L657 ◽  
Author(s):  
Yingjian You ◽  
Tao Huang ◽  
Edward J. Richer ◽  
Jens-Erik Harboe Schmidt ◽  
Joseph Zabner ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Basal Body ◽  
Ciliated Cell ◽  
Airway Epithelial Cells ◽  
Cell Phenotype ◽  
Basal Bodies ◽  
Airway Epithelial ◽  
Ciliated Cells ◽  
Wild Type

Factors required for commitment of an undifferentiated airway epithelial cell to a ciliated cell are unknown. Cell ultrastructure analysis indicates ciliated cell commitment activates a multistage program involving synthesis of cilia precursor proteins and assembly of macromolecular complexes. Foxj1 is an f-box transcription factor expressed in ciliated cells and shown to be required for cilia formation by gene deletion in a mouse model. To identify a specific role for foxj1 in directing the ciliated cell phenotype, we evaluated the capacity of foxj1 to induce ciliogenesis and direct cilia assembly. In a primary culture model of wild-type mouse airway epithelial cells, foxj1 expression preceded the appearance of cilia and in cultured foxj1 null cells cilia did not develop. Delivery of foxj1 to polarized epithelial cell lines and primary cultured alveolar epithelial cells failed to promote ciliogenesis. Similarly, delivery of foxj1 to wild-type airway epithelial cells did not enhance the total number of ciliated cells. In contrast, delivery of foxj1 to null cells resulted in the appearance of cilia. Analysis revealed that, in the absence of foxj1, null cells contained cilia precursor basal bodies, indicating prior commitment to ciliogenesis. However, the basal bodies were disorganized within the apical compartment and failed to dock with the apical membrane. Reconstitution of foxj1 in null cells restored normal basal body organization, resulting in axoneme growth. Thus foxj1 functions in late-stage ciliogenesis to regulate programs promoting basal body docking and axoneme formation in cells previously committed to the ciliated cell phenotype.

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 HIVAN phenotype: consequence of epithelial mesenchymal transdifferentiation

2010 ◽  
Vol 298 (3) ◽  
pp. F734-F744 ◽  
Author(s):  
Anju Yadav ◽  
Sridevi Vallabu ◽  
Dileep Kumar ◽  
Guohua Ding ◽  
Douglas N. Charney ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
De Novo ◽  
Smooth Muscle Actin ◽  
Tissue Expression ◽  
Renal Tissue ◽  
Specific Protein ◽  
Cell Phenotype ◽  
Renal Epithelial Cell

Human immunodeficiency virus (HIV)-1-associated nephropathy (HIVAN) is characterized by proliferation of glomerular and tubular epithelial cells. We studied the role of epithelial mesenchymal transdifferentiation (EMT) in the development of HIVAN phenotype. Renal cortical sections from six FVB/N (control) and six Tg26 (HIVAN) mice were immunolabeled for PCNA, α-smooth muscle actin (α-SMA), fibroblast-specific protein-1 (FSP1), CD3, and F4/80. Since periglomerular cells (PGCs) and peritubular cells (PTCs) did not show any labeling for CD3 and F4/80 but showed labeling for α-SMA or FSP1, it appears that these were myofibroblasts that migrated from either glomerular or tubular sites, respectively. Occurrence of EMT was also supported by diminished expression of E-cadherin by renal epithelial cells in Tg26 mice. Interestingly, Tg26 mice also showed enhanced renal tissue expression of ZEB2; henceforth, it appears that transcription of molecules required for maintenance of de novo renal epithelial cell phenotype was suppressed. To evaluate the role of ANG II, Tg26 mice in groups of three were administered either normal saline or telmisartan (an AT1 receptor blocker) for 2 wk, followed by evaluation for renal cell EMT. Renal cortical section of Tg26 mice showed a sevenfold increase ( P < 0.001) in parietal epithelial cell (PEC)-PGC and a threefold increase ( P < 0.01) in tubular cell (TC)-PTC proliferation (PCNA-positive cells). Similarly, both PECs-PGCs and TCs-PTCs in Tg26 mice showed enhanced expression of α-SMA and FSP1. Both PECs and podocytes contributed to the glomerular proliferative phenotype, but the contribution of PECs was much greater. Telmisartan-receiving Tg26 mice (TRM) showed attenuated number of proliferating PECs-PGCs and TCs-PTCs compared with saline-receiving Tg26 mice (SRM). Similarly, TRM showed diminished expression of α-SMA and FSP1 by both PECs-PGCs and TCs-PTCs compared with SRM. We conclude that EMT contributes to the manifestation of the proliferative phenotype in HIVAN mice.

scholarly journals Podocyte repopulation by renal progenitor cells following glucocorticoids treatment in experimental FSGS

2013 ◽  
Vol 304 (11) ◽  
pp. F1375-F1389 ◽  
Author(s):  
Jiong Zhang ◽  
Jeffrey W. Pippin ◽  
Ronald D. Krofft ◽  
Shokichi Naito ◽  
Zhi-Hong Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Cell Protein ◽  
Abrupt Decrease ◽  
Glomerular Cell ◽  
Renal Progenitor Cells ◽  
Glomerular Epithelial Cells ◽  
Podocyte Loss ◽  
Parietal Epithelial Cell ◽  
Daily Prednisone ◽  
Parietal Epithelial Cells

Prednisone is a mainstay of treatment for patients with focal segmental glomerulosclerosis (FSGS), a disease characterized by reduced podocyte number and glomerulosclerosis. Although the systemic immune-modulatory effects of prednisone are well-known, direct tissue effects on glomerular cells are poorly understood. Experimental FSGS was induced in mice with a cytotoxic anti-podocyte antibody, resulting in an abrupt decrease in podocyte number by day 3, proteinuria, and the development of glomerulosclerosis. Administering daily prednisone to mice with FSGS, beginning at day 3, significantly increased podocyte number at weeks 2 and 4. Podocyte number did not increase in control mice with FSGS given DMSO. The increase in podocyte number in prednisone-treated mice correlated significantly with reduced glomerulosclerosis. Prednisone reduced podocyte apoptosis measured by synaptopodin+/caspase-3+ double staining. Additionally, the number of podocyte progenitors, defined as cells expressing both a parietal epithelial cell protein and a podocyte protein, was significantly increased in prednisone-treated mice with FSGS at weeks 2 and 4. This was associated with increased phospho-ERK staining in both parietal epithelial cells (PAX2+/p-ERK+) and in podocyte progenitors (WT-1+/p-ERK+ lining Bowman's capsule). These data show that in this model of experimental FSGS, prednisone augments glomerular repair by increasing podocyte number through direct effects on both glomerular epithelial cells. Prednisone limits podocyte loss by reducing apoptosis, and it increases regeneration by augmenting the number of podocyte progenitors. The data support a direct glomerular cell action for prednisone in improving outcomes in FSGS.

scholarly journals Modulation of T1α expression with alveolar epithelial cell phenotype in vitro

1998 ◽  
Vol 275 (1) ◽  
pp. L155-L164 ◽  
Author(s):  
Zea Borok ◽  
Spencer I. Danto ◽  
Richard L. Lubman ◽  
Yuxia Cao ◽  
Mary C. Williams ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Cell Shape ◽  
Alveolar Epithelial Cell ◽  
Cell Phenotype ◽  
Alveolar Type ◽  
Type I ◽  
Soluble Factors ◽  
Alveolar Epithelial

T1α is a recently identified gene expressed in the adult rat lung by alveolar type I (AT1) epithelial cells but not by alveolar type II (AT2) epithelial cells. We evaluated the effects of modulating alveolar epithelial cell (AEC) phenotype in vitro on T1α expression using either soluble factors or changes in cell shape to influence phenotype. For studies on the effects of soluble factors on T1α expression, rat AT2 cells were grown on polycarbonate filters in serum-free medium (MDSF) or in MDSF supplemented with either bovine serum (BS, 10%), rat serum (RS, 5%), or keratinocyte growth factor (KGF, 10 ng/ml) from either day 0 or day 4 through day 8 in culture. For studies on the effects of cell shape on T1α expression, AT2 cells were plated on thick collagen gels in MDSF supplemented with BS. Gels were detached on either day 1(DG1) or day 4 (DG4) or were left attached until day 8. RNA and protein were harvested at intervals between days 1 and 8 in culture, and T1α expression was quantified by Northern and Western blotting, respectively. Expression of T1α progressively increases in AEC grown in MDSF ± BS between day 1 and day 8 in culture, consistent with transition toward an AT1 cell phenotype. Exposure to RS or KGF from day 0 prevents the increase in T1α expression on day 8, whereas addition of either factor from day 4 through day 8 reverses the increase. AEC cultured on attached gels express high levels of T1α on days 4 and 8. T1α expression is markedly inhibited in both DG1 and DG4 cultures, consistent with both inhibition and reversal of the transition toward the AT1 cell phenotype. These results demonstrate that both soluble factors and alterations in cell shape modulate T1α expression in parallel with AEC phenotype and provide further support for the concept that transdifferentiation between AT2 and AT1 cell phenotypes is at least partially reversible.

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