Trophoblast glycoprotein: possible candidate mediating podocyte injuries in glomerulonephritis.
BACKGROUND
trophoblast glycoprotein (Tpbg), a 72-kDa transmembrane glycoprotein, is known to regulate the phenotypes of epithelial cells by modifying actin organization and cell motility. Recently, a microarray study showed that Tpbg is upregulated in Thy1 glomerulonephritis (Thy1 GN). We hypothesized that Tpbg regulates cytoskeletal rearrangement and modulates phenotypic alteration in podocytes under pathological conditions.


METHODS
we examined Tpbg expression in Thy1 GN and Tpbg function in mouse podocytes.


RESULTS
we demonstrated that Tpbg is upregulated in the injured podocytes of Thy1 GN. In vitro, immunofluorescence studies revealed that Tpbg colocalized with the focal adhesion protein, vinculin, in parallel with stress fiber formation. This colocalization was observed even when actin filaments were depolymerized with cytochalasin D. Tpbg localization at focal adhesions was induced by dominant-active RhoA and suppressed by the ROCK1 inhibitor Y-26732. In addition, transforming growth factor-β increased Tpbg expression at focal adhesions concurrently with rearrangement of stress fibers. Stress fiber formation was suppressed in differentiated podocytes transfected with full-length Tpbg. Furthermore, knockdown of Tpbg using small interfering RNA decreased podocyte motility.


CONCLUSIONS
our findings suggest a novel role of Tpbg in the phenotypic alteration of injured podocytes, and we accordingly propose a new mechanism of glomerular injury in glomerulonephritis.
Murakami
Taichi
T
Department of Nephrology, Graduate School of Medicine, Institute of Health-Bio-Science, University of Tokushima, Tokushima University Hospital, Tokushima, Japan.
Abe
Hideharu
H
Nagai
Kojiro
K
Tominaga
Tatsuya
T
Takamatsu
Norimichi
N
Araoka
Toshikazu
T
Kishi
Seiji
S
Takahashi
Toshikazu
T
Mima
Akira
A
Takai
Yoshimi
Y
Kopp
Jeffrey B
JB
Doi
Toshio
T
D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D022001:Focal Adhesions / Q000378:metabolism / Q000502:physiology; D015432:Glomerulonephritis, Membranoproliferative / Q000139:chemically induced / Q000473:pathology*; D007518:Isoantibodies; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D023421:Models, Animal; D050199:Podocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D022502:Stress Fibers / Q000502:physiology; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology; D015854:Up-Regulation
D007518:Isoantibodies; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C035678:anti-Thy antibody; C557513:trophoblast glycoprotein, rat