The plant pathogenesis related protein GLIPR-2 is highly expressed in fibrotic kidney and promotes epithelial to mesenchymal transition in vitro.
Fibrosis is the accumulation of extracellular matrix proteins and is a common end pathway in many chronic diseases. To identify novel mediators of fibrosis we used transcript profiling in a mouse model of kidney fibrosis, the COL4A3 knockout (alport) mouse. One gene that we found up-regulated in fibrotic kidney was GLIPR-2, also known as GAPR-1 and C9orf19, a member of the plant pathogenesis-related proteins family 1. We have found that GLIPR-2 protein expression is significantly increased in fibrotic kidney compared to healthy controls. Examination of the expression pattern of GLIPR-2 indicated that the protein is selectively expressed in epithelial cells. Co-staining with antibodies for alpha-smooth muscle actin expression, a marker of myofibroblasts, showed that GLIPR-2 expressing cells are closely apposed to areas of strong alpha-smooth muscle actin expression. The origin of these myofibroblasts is not known, but in vitro studies have shown that GLIPR-2 can induce epithelial to mesenchymal transition (EMT) in a renal epithelial cell line. We propose that increased GLIPR-2 expression in kidney contributes to development of fibrosis by increasing the pool of activated fibroblasts, possibly through the induction of EMT.
Baxter
Ruth M
RM
Department of Research Pathology, Discovery Research and Protein Expression, Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USA. rbaxter@mednet.ucla.edu
Crowell
Thomas P
TP
George
Judith A
JA
Getman
Michael E
ME
Gardner
Humphrey
H
D000199:Actins / Q000378:metabolism; D000818:Animals; D001324:Autoantigens / Q000235:genetics; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D024141:Collagen Type IV / Q000235:genetics; D003239:Connective Tissue Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D007679:Kidney Medulla / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014746:Vimentin / Q000378:metabolism
D000199:Actins; D001324:Autoantigens; D015820:Cadherins; D024141:Collagen Type IV; C519823:GLIPR-2 protein, mouse; C458481:GLIPR2 protein, human; D008565:Membrane Proteins; D011506:Proteins; D014746:Vimentin; C057112:type IV collagen alpha3 chain