The glomerular parietal epithelial cell's responses are influenced by SM22 alpha levels.
BACKGROUND
Studies have shown in several diseases initially affecting podocytes, that the neighboring glomerular parietal epithelial cells (PECs) are secondarily involved. The PEC response might be reparative under certain circumstances, yet injurious under others. The factors governing these are not well understood. We have shown that SM22α, an actin-binding protein considered a marker of smooth muscle differentiation, is upregulated in podocytes and PECs in several models of podocyte disease. However, the impact of SM22α levels on PECs is not known.


METHODS
Experimental glomerular disease, characterized by primary podocyte injury, was induced in aged-matched SM22α+/+ and SM22α-/-mice by intraperitoneal injection of sheep anti-rabbit glomeruli antibody. Immunostaining methods were employed on days 7 and 14 of disease.


RESULTS
The number of PEC transition cells, defined as cells co-expressing a PEC protein (PAX2) and podocyte protein (Synaptopodin) was higher in diseased SM22α-/-mice compared with SM22α+/+mice. WT1 staining along Bowman's capsule is higher in diseased SM22α-/-mice. This was accompanied by increased PEC proliferation (measured by ki-67 staining), and an increase in immunostaining for the progenitor marker NCAM, in a subpopulation of PECs in diseased SM22α-/-mice. In addition, immunostaining for vimentin and alpha smooth muscle actin, markers of epithelial-to-mesenchymal transition (EMT), was lower in diseased SM22α-/-mice compared to diseased SM22α+/+mice.


CONCLUSIONS
SM22α levels may impact how PECs respond following a primary podocyte injury in experimental glomerular disease. Absent/lower levels favor an increase in PEC transition cells and PECs expressing a progenitor marker, and a lower EMT rate compared to SM22α+/+mice, where SM22 levels are markedly increased in PECs.
Shokichi
S
Naito
Jeffrey W
JW
Pippin
Division of Nephrology Department of Medicine, University of Washington School of Medicine, Box 356521, 1959 NE Pacific St,, Seattle, WA 98195-6521, USA. stuartjs@u.washington.edu.
Stuart J
SJ
Shankland
D000199:Actins / Q000032:analysis; D000818:Animals; D050476:Bowman Capsule / Q000648:ultrastructure; D019002:CD56 Antigen / Q000032:analysis; D002454:Cell Differentiation; D002455:Cell Division; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D005921:Glomerulonephritis / Q000378:metabolism / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000032:analysis / Q000172:deficiency / Q000502:physiology*; D009124:Muscle Proteins / Q000172:deficiency / Q000502:physiology*; D051762:PAX2 Transcription Factor / Q000032:analysis; D050199:Podocytes / Q000737:chemistry / Q000473:pathology; D011897:Random Allocation; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D014746:Vimentin / Q000032:analysis
D000199:Actins; D019002:CD56 Antigen; D008840:Microfilament Proteins; D009124:Muscle Proteins; C501063:Ncam1 protein, mouse; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; C503968:Synpo protein, mouse; C058992:Tagln protein, mouse; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D014746:Vimentin