scholarly journals Podocyte-specific KLF4 is required to maintain parietal epithelial cell quiescence in the kidney

2021 ◽  
Vol 7 (36) ◽  
Author(s):  
Jesse A. Pace ◽  
Robert Bronstein ◽  
Yiqing Guo ◽  
Yaqi Yang ◽  
Chelsea C. Estrada ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Quiescence ◽  
Parietal Epithelial Cell

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.

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.

scholarly journals The metalloproteinase Papp-aa controls epithelial cell quiescence-proliferation transition

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Chengdong Liu ◽  
Shuang Li ◽  
Pernille Rimmer Noer ◽  
Kasper Kjaer-Sorensen ◽  
Anna Karina Juhl ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Tor Signaling ◽  
Mineral Density ◽  
Zebrafish Model ◽  
Bone Mass Loss ◽  
Cell Quiescence ◽  
Underlying Mechanisms ◽  
Igf1 Receptor ◽  
Bone Calcification ◽  
Igf Signaling

Human patients carrying PAPP‐A2 inactivating mutations have low bone mineral density. The underlying mechanisms for this reduced calcification are poorly understood. Using a zebrafish model, we report that Papp-aa regulates bone calcification by promoting Ca2+-transporting epithelial cell (ionocyte) quiescence-proliferation transition. Ionocytes, which are normally quiescent, re-enter the cell cycle under low [Ca2+] stress. Genetic deletion of Papp-aa, but not the closely related Papp-ab, abolished ionocyte proliferation and reduced calcified bone mass. Loss of Papp-aa expression or activity resulted in diminished IGF1 receptor-Akt-Tor signaling in ionocytes. Under low Ca2+ stress, Papp-aa cleaved Igfbp5a. Under normal conditions, however, Papp-aa proteinase activity was suppressed and IGFs were sequestered in the IGF/Igfbp complex. Pharmacological disruption of the IGF/Igfbp complex or adding free IGF1 activated IGF signaling and promoted ionocyte proliferation. These findings suggest that Papp-aa-mediated local Igfbp5a cleavage functions as a [Ca2+]-regulated molecular switch linking IGF signaling to bone calcification by stimulating epithelial cell quiescence-proliferation transition under low Ca2+ stress.

scholarly journals Author response: The metalloproteinase Papp-aa controls epithelial cell quiescence-proliferation transition

2020 ◽  
Author(s):  
Chengdong Liu ◽  
Shuang Li ◽  
Pernille Rimmer Noer ◽  
Kasper Kjaer-Sorensen ◽  
Anna Karina Juhl ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Author Response ◽  
Cell Quiescence
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