title: Parietal epithelial cells participate in the formation of sclerotic lesions in focal segmental glomerulosclerosis.
abstract: The pathogenesis of the development of sclerotic lesions in focal segmental glomerulosclerosis (FSGS) remains unknown. Here, we selectively tagged podocytes or parietal epithelial cells (PECs) to determine whether PECs contribute to sclerosis. In three distinct models of FSGS (5/6-nephrectomy + DOCA-salt; the murine transgenic chronic Thy1.1 model; or the MWF rat) and in human biopsies, the primary injury to induce FSGS associated with focal activation of PECs and the formation of cellular adhesions to the capillary tuft. From this entry site, activated PECs invaded the affected segment of the glomerular tuft and deposited extracellular matrix. Within the affected segment, podocytes were lost and mesangial sclerosis developed within the endocapillary compartment. In conclusion, these results demonstrate that PECs contribute to the development and progression of the sclerotic lesions that define FSGS, but this pathogenesis may be relevant to all etiologies of glomerulosclerosis.
authors: Department of Nephrology and Clinical Immunology, RWTH University Hospital Aachen, Pauwelsstr. 30, 52074 Aachen, Germany.
authors: Bart
authors: B
authors: Smeets
authors: Christoph
authors: C
authors: Kuppe
authors: Eva-Maria
authors: EM
authors: Sicking
authors: Astrid
authors: A
authors: Fuss
authors: Peggy
authors: P
authors: Jirak
authors: Toin H
authors: TH
authors: van Kuppevelt
authors: Karlhans
authors: K
authors: Endlich
authors: Jack F M
authors: JF
authors: Wetzels
authors: Hermann-Josef
authors: HJ
authors: Gröne
authors: Jürgen
authors: J
authors: Floege
authors: Marcus J
authors: MJ
authors: Moeller
mesh_terms: D000818:Animals; D019070:Cell Lineage; D003900:Desoxycorticosterone; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology* / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009392:Nephrectomy; D050199:Podocytes / Q000473:pathology*; D051381:Rats; D017673:Sodium Chloride, Dietary; D018800:Thy-1 Antigens / Q000235:genetics
chemical_list: C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D017673:Sodium Chloride, Dietary; D018800:Thy-1 Antigens; D003900:Desoxycorticosterone