dc.contributor.author | Lin, S | |
dc.contributor.author | Visram, F | |
dc.contributor.author | Liu, W | |
dc.contributor.author | Haig, A | |
dc.contributor.author | Jiang, J | |
dc.contributor.author | Mok, A | |
dc.contributor.author | Lian, D | |
dc.contributor.author | Wood, ME | |
dc.contributor.author | Torregrossa, R | |
dc.contributor.author | Whiteman, M | |
dc.contributor.author | Lobb, I | |
dc.contributor.author | Sener, A | |
dc.date.accessioned | 2016-06-07T13:04:20Z | |
dc.date.issued | 2016-05-10 | |
dc.description.abstract | PURPOSE: Chronic obstructive uropathy can cause irreversible kidney injury, atrophy, and inflammation, which can ultimately lead to fibrosis. Epithelial-mesenchymal transition (EMT) is a key trigger of fibrosis and is caused by upregulation of transforming growth factor beta 1 (TGF-β1) and angiotensin II (ANGII). Hydrogen sulfide (H2S) is an endogenously produced gasotransmitter with cytoprotective properties. The present study aims to elucidate the effects of the slow-releasing H2S donor GYY4137 on chronic ureteral obstruction and evaluate potential mechanisms. MATERIALS AND METHODS: Following unilateral ureteral obstruction (UUO), male Lewis rats were given daily intraperitoneal (IP) administration of phosphate buffered saline (PBS) vehicle (UUO group) or PBS+200μmol/kg GYY4137 (UUO+GYY4137 group) for 30 days. Urine and serum samples were collected to determine physiological parameters of renal function and injury. Kidneys were removed on post-operative day 30 for evaluation of histopathology and protein expression. EMT in pig kidney epithelial cells (LLC-PK1) was induced with TGF-β1 and treated with GYY4137 to evaluate potential mechanisms via in vitro scratch wound assays. RESULTS: H2S treatment decreased serum creatinine and urine protein/creatinine excretion ratio following UUO. In addition, H2S mitigated cortical loss, inflammatory damage, and tubulointerstitial fibrosis. Tissues exhibited decreased expression of EMT markers upon H2S treatment. EMT progression in LLC-PK1 was alleviated upon in vitro administration of GYY4137. CONCLUSIONS: Our findings demonstrate, for the first time, the protective effects of H2S in chronic obstructive uropathy and may represent a potential therapeutic solution to ameliorate renal damage and improve clinical outcomes of urinary obstruction. | en_GB |
dc.description.sponsorship | This work was supported by a grant from the Lawson Health Research Foundation. | en_GB |
dc.identifier.doi | 10.1016/j.juro.2016.05.029 | |
dc.identifier.uri | http://hdl.handle.net/10871/21878 | |
dc.language.iso | en | en_GB |
dc.publisher | Elsevier | en_GB |
dc.relation.url | http://www.ncbi.nlm.nih.gov/pubmed/27177428 | en_GB |
dc.rights.embargoreason | Publisher policy | en_GB |
dc.rights | This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record. | en_GB |
dc.subject | Angiotensin II | en_GB |
dc.subject | Chronic obstructive uropathy | en_GB |
dc.subject | Epithelial-mesenchymal transition | en_GB |
dc.subject | Hydrogen sulfide | en_GB |
dc.subject | Transforming growth factor β-1 | en_GB |
dc.title | GYY4137, a slow-releasing hydrogen sulfide donor, ameliorates renal damage associated with chronic obstructive uropathy. | en_GB |
dc.type | Article | en_GB |
dc.identifier.issn | 0022-5347 | |
dc.identifier.journal | The Journal of Urology | en_GB |