Escherichia coli-human uroepithelial cell interaction products enhance fibroblast migration and matrix accumulation.
OBJECTIVE
Urinary tract infection has been associated with renal interstitial scarring and ureteral wall fibrosis. The mechanism of progression of scarring despite attenuation of the primary insult is not clear. We examined the role of the products of the interaction between Escherichia coli and human uroepithelial cells (HUC-EC-S) on the migration of fibroblasts, as well as their matrix synthesis.


METHODS
We evaluated the effect of HUC-EC-S (concentration of 10%, 15%, and 25%) on the migration of fibroblasts across a filter in a modified Boyden chamber. To determine the role of transforming growth factor-beta and MCP-1, we studied the effect of anti-TGF-beta and anti-MCP-1 antibodies on interaction product-induced fibroblast migration. The effect of HUC-EC-S on fibronectin and collagen I accumulation was studied by the Western blotting.


RESULTS
Bacterial-HUC interaction products enhanced (P < 0.001) migration of fibroblasts compared with uroepithelial interaction product (HUC-S). Anti-TGF-beta and anti-MCP-1 antibodies partly inhibited (P < 0.001) the HUC-EC-S-induced fibroblast migration. Also, HUC-EC-S-treated fibroblasts showed enhanced accumulation of fibronectin and collagen 1.


CONCLUSIONS
Escherichia coli-induced activation of HUC not only promotes migration of fibroblasts but also triggers matrix remodeling.
Kapoor
R
R
Department of Urology, Albert Einstein College of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11040, USA.
Reddy
K
K
Liatsikos
E N
EN
Smith
A D
AD
Singhal
P C
PC
D000906:Antibodies / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000276:immunology; D004926:Escherichia coli / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D016212:Transforming Growth Factor beta / Q000276:immunology; D053773:Transforming Growth Factor beta1; D019459:Urothelium / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology*
D000906:Antibodies; D018932:Chemokine CCL2; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1