Transforming growth factor β-induced peritoneal fibrosis is mouse strain dependent.
BACKGROUND
Encapsulating peritoneal sclerosis (EPS) is a rare but devastating complication of peritoneal dialysis. The etiology is unclear, but genetic predisposition may be a contributing factor. We used adenovirus-mediated gene transfer of transforming growth factor (TGF) β1 to the peritoneum in four genetically distinct laboratory mouse strains to assess differences in fibrogenic response.


METHODS
Mice from four genetic backgrounds (C57BL/6J, DBA/2J, C3H/HeJ and SJL/J) received an intraperitoneal injection of an adenovirus expressing TGFβ1 (AdTGFβ1) or control adenovirus (AdDL) and were assessed 4 and 10 days after infection. Submesothelial thickening, angiogenesis and gene expression were quantified from peritoneal tissue. Protein was extracted from omental tissue and assessed for collagen, E-cadherin and TGFβ signaling pathway proteins.


RESULTS
There was a graded response among the mouse strains to the peritoneal overexpression of TGFβ1. TGFβ1 induced a significant fibrogenic response in the C57BL/6J mice, whereas the SJL/J mice were resistant. The DBA/2J and the C3H/HeJ mice had intermediate responses. A similar graded response was seen in collagen protein levels in the omental tissue and in fibrosis-associated gene expression. TGFβ type 1 receptor and SMAD signaling pathways appeared to be intact in all the mouse strains.


CONCLUSIONS
There were significant differences in mouse strain susceptibility to peritoneal fibrosis, suggesting that genetic factors may play a role in the development of peritoneal fibrosis and possibly EPS. As early TGFβ1 signaling mechanisms appear to be intact, we hypothesize that fibrosis resistance in the SJL/J mice lies further down the wound-healing cascade or in an alternate, non-SMAD pathway.
Department of Nephrology, McMaster University, Hamilton, Ontario, Canada.
Peter J
PJ
Margetts
Catherine
C
Hoff
Limin
L
Liu
Ron
R
Korstanje
Louise
L
Walkin
Angela
A
Summers
Sarah
S
Herrick
Paul
P
Brenchley
D000818:Animals; D007274:Injections, Intraperitoneal; D007674:Kidney Diseases / Q000150:complications*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D056627:Peritoneal Fibrosis / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D051785:Smad Proteins / Q000378:metabolism; D013045:Species Specificity; D016212:Transforming Growth Factor beta / Q000009:adverse effects*
D051785:Smad Proteins; D016212:Transforming Growth Factor beta