Differential Expression of Parietal Epithelial Cell and Podocyte Extracellular Matrix Proteins in Focal Segmental Glomerulosclerosis and Diabetic Nephropathy.

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 LAMB2 and Agrin in PECs. Similar findings were observed in biopsies from patients with FSGS and DN. Increases in individual ECM proteins co-localized with CD44 in PECs in disease. To determine the role of CD44, FSGS was induced in CD44-/- and CD44+/+ mice. PEC staining for Perlecan, COL4A2, LAMB2 and Agrin were significantly lower in diseased CD44-/- mice compared to 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. PMID: 31630546 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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