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[PMID]: | 29522906 | [Au] Autor: | Lin S; Lian D; Liu W; Haig A; Lobb I; Hijazi A; Razvi H; Burton J; Whiteman M; Sener A |
[Ad] Address: | Department of Microbiology and Immunology, Western University, London, Ontario, Canada; Matthew Mailing Center for Translational Transplant Studies, London Health Sciences Center, London, Ontario, Canada. | [Ti] Title: | Daily therapy with a slow-releasing H S donor GYY4137 enables early functional recovery and ameliorates renal injury associated with urinary obstruction. | [So] Source: | Nitric Oxide;, 2018 Mar 06. | [Is] ISSN: | 1089-8611 | [Cp] Country of publication: | United States | [La] Language: | eng | [Ab] Abstract: | OBJECTIVES: To assess the effects of slow-releasing H S donor GYY4137 on post-obstructive renal function and injury following unilateral ureteral obstruction (UUO) by using the UUO and reimplantation (UUO-R) model in rats and to elucidate potential mechanisms by using an in vitro model of epithelial-mesenchymal transition (EMT). METHODS: Male Lewis rats underwent UUO at the left ureterovesical junction. From post-obstructive day (POD) 1-13, rats received daily intraperitoneal (IP) injection of phosphate buffered saline (PBS, 1 mL) or GYY4137 (200 µmol/kg/day in 1 mL PBS, IP). On POD 14, the ureter was reimplanted back into the bladder, followed by a right nephrectomy. Urine and serum samples were collected to monitor renal function. On POD 30, the left kidney was removed and tissue sections were stained with H&E, TUNEL, CD68, CD206, myeloperoxidase, and Masson's trichrome to determine cortical thickness, apoptosis, inflammation, and fibrosis. In our in vitro model of EMT, NRK52E cells were treated with 10 ng/mL TGF-ß1, 10 µM GYY4137 and/or 50 µM GYY4137. Western blot analysis was performed to determine the expression of E-cadherin, vimentin, Smad7 and TGF-ß1 receptor II (TßRII). RESULTS: GYY4137 led to a moderate decrease in post-obstructive serum creatinine, cystatin C and FENa. We also observed a trend towards a decrease in post-obstructive proteinuria following GYY4137 treatment. Histologically, we observed a significant decrease in apoptosis, inflammation, and fibrosis. Furthermore, our in vitro studies demonstrate that in the presence of TGF-ß1, GYY4137 significantly decreases vimentin and TßRII and significantly increases E-cadherin and Smad7. CONCLUSIONS: H S may help to accelerate the recovery of renal function post-obstruction and attenuates renal injury associated with UUO. It is possible that H S mitigates fibrosis by regulating the TGF-ß1-mediated EMT pathway. Taken together, our data suggest that H S may be a potential novel therapy for improving renal function and limiting renal injury associated with obstructive uropathy. | [Pt] Publication type: | JOURNAL ARTICLE | [Em] Entry month: | 1803 | [Cu] Class update date: |
180309 | [Lr] Last revision date: | 180309 | [St] Status: | Publisher |
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