PMID- 15297261 OWN - NLM STAT- MEDLINE DCOM- 20050308 LR - 20211203 IS - 0193-1857 (Print) IS - 0193-1857 (Linking) VI - 288 IP - 1 DP - 2005 Jan TI - The gene transfer of soluble VEGF type I receptor (Flt-1) attenuates peritoneal fibrosis formation in mice but not soluble TGF-beta type II receptor gene transfer. PG - G143-50 AB - Peritoneal fibrosis formation is a consequence of inflammation/injury and a significant medical problem to be solved. The effects of soluble VEGF receptor type I (sFlt-1) gene transfer on experimental peritoneal fibrosis were examined and compared with soluble transforming growth factor-beta (TGF-beta) receptor type II (sTGF beta RII) gene transfer. Male C57BL/6 mice were injected with 1.5 x 10(8) plaque-forming unit of adenovirus encoding active TGF-beta (AdTGF beta) intraperitoneally. Some mice had been treated with sTGF betaRII or sFlt-1 plasmid injection into skeletal muscle with electroporation 4 days before virus administration. Mice were euthanized at day 14 after virus administration. AdTGF beta induced significant elevation of serum active TGF-beta, caused significant inflammatory response [weight loss, elevation of serum amyloid-P (SAP) and IL-12, increased expression of monocyte chemoattractant protein-1 (MCP-1) mRNA], and induced marked thickening of the peritoneum and collagen deposition. Gene transfer of sFlt-1 reduced the collagen deposition approximately 81% in mesenteric tissue. Treatment with sFlt-1 decreased ICAM-1 and MCP-1 mRNA expression significantly. Significant negative correlation between serum sFlt-1 and placental growth factor level was observed, whereas there was no significant negative correlation between sFlt-1 and VEGF. On the other hand, sTGF beta RII treatment enhanced the AdTGF beta-induced inflammation (significant elevation of SAP, TNF-alpha, and IL-12 levels and upregulation of ICAM-1 and MCP-1 mRNA expressions) and failed to prevent collagen deposition. These observations indicate that sFlt-1 gene transfer might be of therapeutic benefit in peritoneal fibrosis. FAU - Motomura, Y AU - Motomura Y AD - Intestinal Disease Research Programme, McMaster University, Hamilton, Ontario L8N 3Z5, Canada. FAU - Kanbayashi, H AU - Kanbayashi H FAU - Khan, W I AU - Khan WI FAU - Deng, Y AU - Deng Y FAU - Blennerhassett, P A AU - Blennerhassett PA FAU - Margetts, P J AU - Margetts PJ FAU - Gauldie, J AU - Gauldie J FAU - Egashira, K AU - Egashira K FAU - Collins, S M AU - Collins SM LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20040805 PL - United States TA - Am J Physiol Gastrointest Liver Physiol JT - American journal of physiology. Gastrointestinal and liver physiology JID - 100901227 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Receptors, Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type II) SB - IM MH - Animals MH - Chemokine CCL2/biosynthesis MH - Fibrosis MH - *Gene Transfer Techniques MH - Inflammation MH - Intercellular Adhesion Molecule-1/biosynthesis MH - Mice MH - Mice, Inbred C57BL MH - Peritoneum/*pathology MH - Protein Serine-Threonine Kinases MH - Receptor, Transforming Growth Factor-beta Type II MH - Receptors, Transforming Growth Factor beta/*physiology MH - Transforming Growth Factor beta MH - Up-Regulation MH - Vascular Endothelial Growth Factor Receptor-1/*genetics/*physiology EDAT- 2004/08/07 05:00 MHDA- 2005/03/09 09:00 CRDT- 2004/08/07 05:00 PHST- 2004/08/07 05:00 [pubmed] PHST- 2005/03/09 09:00 [medline] PHST- 2004/08/07 05:00 [entrez] AID - 00186.2004 [pii] AID - 10.1152/ajpgi.00186.2004 [doi] PST - ppublish SO - Am J Physiol Gastrointest Liver Physiol. 2005 Jan;288(1):G143-50. doi: 10.1152/ajpgi.00186.2004. Epub 2004 Aug 5.