HSP-mediated cytoprotection of mesothelial cells in experimental acute peritoneal dialysis.
BACKGROUND
Low biocompatibility of peritoneal dialysis solution (PDS) injures mesothelial cells but also induces heat shock proteins (HSP), the main effectors of the cellular stress response. This study investigated whether overexpression of HSP upon pharmacologic induction results in cytoprotection of mesothelial cells in experimental PD.


METHODS
Stress response of mesothelial cells upon exposure to PDS was pharmacologically manipulated using glutamine as a co-inducer. In vitro, HSP-mediated cytoprotection was assessed by simultaneous measurements of HSP expression using Western blot analysis and viability testing using release of lactic dehydrogenase in cultured human mesothelial cells. In vivo, detachment of mesothelial cells from their peritoneal monolayer was assessed following exposure to PDS with and without the addition of glutamine in the acute rat model of PD.


RESULTS
In vitro, mesothelial cell viability following exposure to PDS was significantly improved upon pharmacologic co-induction of HSP expression by glutamine (226% +/- 29% vs 190% +/- 19%, p = 0.001). In vivo, mesothelial cell detachment during exposure to PDS was reduced upon pharmacologic induction of HSP expression by glutamine (93 +/- 39 vs 38 +/- 38 cells, p = 0.044), resulting in reduced peritoneal protein loss (75 +/- 7 vs 65 +/- 4 mg, p = 0.045).


CONCLUSIONS
Our results represent the first study of pharmacologic manipulation of HSP expression for cytoprotection of mesothelial cells following acute in vitro and in vivo exposure to PDS. PDS with added glutamine might represent a promising therapeutic approach against low biocompatibility of PDS but needs validation in a chronic PD model.
Department of Pediatrics, Medical University, Vienna, Austria.
Thorsten O
TO
Bender
Michael
M
Böhm
Klaus
K
Kratochwill
Hans
H
Lederhuber
Michaela
M
Endemann
Bettina
B
Bidmon
Christoph
C
Aufricht
D000818:Animals; D019610:Cytoprotection / Q000187:drug effects*; D015314:Dialysis Solutions; D004848:Epithelium / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D005973:Glutamine / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010530:Peritoneal Dialysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D015314:Dialysis Solutions; D006360:Heat-Shock Proteins; D005973:Glutamine