BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is one of the most common patterns of glomerular injury encountered in human renal biopsies. Epithelial hyperplasia, which can be prominent in FSGS, has been attributed to dedifferentiation and proliferation of podocytes. Based on observations in a mouse model of FSGS, we pointed to the role of parietal epithelial cells (PECs). In the present study we investigated the relative role of PECs and podocytes in human idiopathic FSGS. METHODS: We performed a detailed study of lesions from a patient with recurrent idiopathic FSGS by serial sectioning, marker analysis and three-dimensional reconstruction of glomeruli. We have studied the expression of markers for podocytes, PECs, mesangial cells, endothelium, and myofibroblasts. We also looked at proliferation and composition of the deposited extracellular matrix (ECM). RESULTS: We found that proliferating epithelial cells in FSGS lesions are negative for podocyte and macrophage markers, but stain for PEC markers. The composition of the matrix deposited by these cells is identical to Bowman's capsule. CONCLUSION: Our study demonstrates that PECs are crucially involved in the pathogenesis of FSGS lesions.
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is one of the most common patterns of glomerular injury encountered in human renal biopsies. Epithelial hyperplasia, which can be prominent in FSGS, has been attributed to dedifferentiation and proliferation of podocytes. Based on observations in a mouse model of FSGS, we pointed to the role of parietal epithelial cells (PECs). In the present study we investigated the relative role of PECs and podocytes in human idiopathic FSGS. METHODS: We performed a detailed study of lesions from a patient with recurrent idiopathic FSGS by serial sectioning, marker analysis and three-dimensional reconstruction of glomeruli. We have studied the expression of markers for podocytes, PECs, mesangial cells, endothelium, and myofibroblasts. We also looked at proliferation and composition of the deposited extracellular matrix (ECM). RESULTS: We found that proliferating epithelial cells in FSGS lesions are negative for podocyte and macrophage markers, but stain for PEC markers. The composition of the matrix deposited by these cells is identical to Bowman's capsule. CONCLUSION: Our study demonstrates that PECs are crucially involved in the pathogenesis of FSGS lesions.
Authors: Bart Smeets; Sandra Uhlig; Astrid Fuss; Fieke Mooren; Jack F M Wetzels; Jürgen Floege; Marcus J Moeller Journal: J Am Soc Nephrol Date: 2009-11-16 Impact factor: 10.121
Authors: Takamoto Ohse; Jeffrey W Pippin; Alice M Chang; Ronald D Krofft; Jeffrey H Miner; Michael R Vaughan; Stuart J Shankland Journal: Kidney Int Date: 2009-10-21 Impact factor: 10.612
Authors: Bart Smeets; Christoph Kuppe; Eva-Maria Sicking; Astrid Fuss; Peggy Jirak; Toin H van Kuppevelt; Karlhans Endlich; Jack F M Wetzels; Hermann-Josef Gröne; Jürgen Floege; Marcus J Moeller Journal: J Am Soc Nephrol Date: 2011-06-30 Impact factor: 10.121
Authors: Christoph Kuppe; Hermann-Josef Gröne; Tammo Ostendorf; Toin H van Kuppevelt; Peter Boor; Jürgen Floege; Bart Smeets; Marcus J Moeller Journal: Kidney Int Date: 2015-04-08 Impact factor: 10.612