Parietal Epithelial Cells Participate in the Formation of Sclerotic Lesions in Focal Segmental Glomerulosclerosis | Zendy

Bart Smeets | Zendy; Christoph Kuppe | Zendy; Eva-Maria Sicking | Zendy; Astrid Fuss | Zendy; Peggy Jirak | Zendy; Toin H. Van Kuppevelt | Zendy; Karlhans Endlich | Zendy; Jack F.M. Wetzels | Zendy; Hermann-Josef Gröne | Zendy; Jürgen Floege | Zendy; Marcus J. Moeller | Zendy

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Parietal Epithelial Cells Participate in the Formation of Sclerotic Lesions in Focal Segmental Glomerulosclerosis

Author(s) -

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

Publication year - 2011

Publication title -

journal of the american society of nephrology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 4.451

H-Index - 279

eISSN - 1533-3450

pISSN - 1046-6673

DOI - 10.1681/asn.2010090970

Subject(s) - glomerulosclerosis , focal segmental glomerulosclerosis , pathology , pathogenesis , podocyte , medicine , extracellular matrix , genetically modified mouse , glomerulonephritis , biology , kidney , transgene , proteinuria , microbiology and biotechnology , biochemistry , gene

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.

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