scholarly journals Sestrin 2: a regulator of the glomerular parietal epithelial cell phenotype

2014 ◽  
Vol 307 (7) ◽  
pp. F798-F799 ◽  
Author(s):  
Bart Smeets ◽  
Tobias B. Huber
Keyword(s):  
Epithelial Cell ◽  
Cell Phenotype ◽  
Parietal Epithelial Cell

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.

Glomerular Outgrowth as an Ex Vivo Assay to Analyze Pathways Involved in Parietal Epithelial Cell Activation

10.3791/60324 ◽  
2020 ◽  
Author(s):  
Jennifer Eymael ◽  
Laura Miesen ◽  
Fieke Mooren ◽  
Jitske Jansen ◽  
Jack Wetzels ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Activation ◽  
Ex Vivo ◽  
Parietal Epithelial Cell ◽  
Ex Vivo Assay

scholarly journals Differential expression of parietal epithelial cell and podocyte extracellular matrix proteins in focal segmental glomerulosclerosis and diabetic nephropathy

2019 ◽  
Vol 317 (6) ◽  
pp. F1680-F1694 ◽  
Author(s):  
Gek Cher Chan ◽  
Diana G. Eng ◽  
Jeffrey H. Miner ◽  
Charles E. Alpers ◽  
Kelly Hudkins ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Diabetic Nephropathy ◽  
Epithelial Cell ◽  
Focal Segmental Glomerulosclerosis ◽  
Collagen Type ◽  
Collagen Type Iv ◽  
Type Iv ◽  
Ecm Proteins ◽  
Segmental Glomerulosclerosis ◽  
Parietal Epithelial Cell

In healthy glomeruli, parietal epithelial cell (PEC)-derived extracellular matrix (ECM) proteins include laminin-β1, perlecan, and collagen type IV-α2 and podocyte-specific ECM proteins include laminin-β2, agrin, and collagen type IV-α4. This study aimed to define individual ECM protein isoform expression by PECs in both experimental and human focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy (DN) and to determine if changes were CD44 dependent. In experimental FSGS induced with a cytotoxic podocyte antibody and in the BTBR ob/ob mouse model of DN, PEC-derived protein staining was significantly increased in PECs. Dual staining also showed de novo expression of the podocyte-specific ECM proteins laminin-β2 and agrin in PECs. Similar findings were observed in biopsies from patients with FSGS and DN. Increases in individual ECM proteins colocalized with CD44 in PECs in disease. To determine the role of CD44, FSGS was induced in CD44−/− and CD44+/+ mice. PEC staining for perlecan, collagen type IV-α2, laminin-β2, and agrin were significantly lower in diseased CD44−/− mice compared with diseased CD44+/+ mice. These results show that in experimental and human FSGS and DN, PECs typically in an activated state, produce both PEC-derived and podocyte-specific ECM protein isoforms, and that the majority of these changes were dependent on CD44.

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.

SuO007CYCLOPHILINS A AND B OPPOSITELY REGULATE RENAL TUBULAR EPITHELIAL CELL PHENOTYPE

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Eduard Sarró ◽  
Mónica Durán ◽  
Ana Rico ◽  
Anthony Croatt ◽  
Karl Nath ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Tubular Epithelial Cell ◽  
Cell Phenotype ◽  
Renal Tubular Epithelial Cell ◽  
Renal Tubular

scholarly journals Maintenance of human amnion epithelial cell phenotype in pulmonary surfactant

2014 ◽  
Vol 5 (5) ◽  
pp. 107 ◽  
Author(s):  
Courtney A McDonald ◽  
Jacqueline M Melville ◽  
Graeme R Polglase ◽  
Graham Jenkin ◽  
Timothy JM Moss
Keyword(s):  
Epithelial Cell ◽  
Pulmonary Surfactant ◽  
Cell Phenotype ◽  
Human Amnion

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.

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