The authors can only speculate that in the studies conducted here, PECs serve to differentiate into podocytes under certain conditions, which remain poorly defined

The authors can only speculate that in the studies conducted here, PECs serve to differentiate into podocytes under certain conditions, which remain poorly defined. mice. These results are consistent with Tetradecanoylcarnitine glomerular cells coexpressing podocyte and PEC proteins in experimental glomerular disease, but not under normal circumstances. Keywords: glomerulonephritis, differentiation, phenotype, FSGS, membranous nephropathy a large body of evidence shows that the terminally differentiated epithelial cells called podocytes have a vey low proliferative capacity (15, 25, 32, 34). This is one of the major reasons underlying the decline in overall podocyte number in experimental and human glomerular diseases that are characterized by podocyte detachment and/or apoptosis. Reduced podocyte number prospects to proteinuria and glomerular scarring (33). Similarly, in many disease says, podocytes are unable to maintain their highly specialized phenotype and begin to lose expression of the proteins that define their function (5, 12, 14, 18, 20, 27, 31, 35, 37, 38). These observations raise several questions: are there conditions under which podocyte replenishment occurs when podocytes are lost, and if so, what is the cellular precursor of these regenerating podocytes? When podocytes drop their specialized phenotype, are they able to regain it? Parietal epithelial cells (PECs) have received recent attention as they and podocytes share a common lineage until the S-shaped stage of glomerulogenesis. Between the S-shaped Tetradecanoylcarnitine body and capillary loop stages, PECs and STAT6 podocytes begin to express unique genes specific to each cell’s function. In podocytes, the transcription factor Wilms’ tumor 1 (WT-1) and the actin cytoskeleton linking the protein synaptopodin are expressed exclusively in the podocyte at this stage. In PECs, the transcription factor paired box gene 8 (PAX8) and the tight junction protein claudin 1 are expressed during this stage (21, 22). Thereafter. these proteins are constitutively expressed in each cell type in mature glomeruli and contribute to functional characteristics of each cell type. Both the shared common lineage between PECs and podocytes and the close proximity of PECs to podocytes make PECs good potential candidates as podocyte precursors. Moreover, some have suggested the presence of unique cells called parietal podocytes (4, 8). In contrast to podocytes, PECs readily proliferate in certain forms Tetradecanoylcarnitine of glomerular disease. More recently, studies by Appel et al. (2) shed new light on the notion of Tetradecanoylcarnitine a local podocyte precursor function for PECs in the developing kidney. In the current studies, we sought to determine whether following injury, PECs express podocyte-specific proteins and/or whether following injury, podocytes express PEC proteins. Four models of experimental glomerular diseases were analyzed. METHODS Animal studies. Four types of animal models were examined in this study. First, the transforming growth factor (TGF)-1 transgenic mouse has been previously explained (30). The alb/TGF-1 mice carry a construct with constitutively activated TGF-1 (protein sequence identical between mouse and human) under the control of the murine albumin promoter, resulting in elevated circulating plasma levels of active TGF-1 as early as 2 wk of age, podocyte injury at 2 wk of age, and glomerulosclerosis at 3 wk of age. Alb/TGF-1 mice and control C57Bl6 X CBA mice were maintained at the animal care facilities at the National Institutes of Health under a protocol approved by the Animal Care and Use Committee, according to = 8/group), following a protocol that was a modification of methods previously described (6, 7). For predictable and reproducible induction of sustained proteinuria and progressive glomerulosclerosis, two doses, separated by 4 wk, were utilized in our studies. Control animals.