Renoprotective mechanisms of telmisartan on renal injury and inflammation in SHRSP.Z-Leprfa/IzmDmcr rats.

Abstract

BACKGROUND:

SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP fatty) rats create a new animal model of metabolic syndrome. However, the renoprotective effect of telmisartan therapy and its underlying mechanisms in SHRSP fatty rats remain unknown. We evaluate the effects of long-term telmisartan therapy on renal dysfunction, podocyte injury, inflammation, and transforming growth factor-β1 (TGF-β1)/Smad, epithelial-mesenchymal transition (EMT), mitogen-activated protein kinase (MAPK), Rho-kinase, and cell-cycle progression pathway in the renal cortex of SHRSP fatty rats.

METHODS:

Seven-week-old male SHRSP fatty rats were treated with vehicle, telmisartan, and hydralazine for 8 weeks. Age-matched male Wistar-Kyoto/Izumo rats served as a control group.

RESULTS:

Vehicle-treated SHRSP fatty rats developed proteinuria and renal dysfunction, which in the telmisartan group was less than the vehicle and hydralazine group without changing blood pressure. Glomerulosclerosis and interstitial fibrosis were impaired in SHRSP fatty rats, and the renal damage in the telmisartan group was less than the vehicle and hydralazine groups. Decreased expression of nephrin and podocin and increased desmin-positive area in SHRSP fatty rats were restored by telmisartan but not hydralazine. TGF-β1/Smad, EMT marker, MAPK, Rho-kinase, and cell-cycle progression pathways were upregulated in SHRSP fatty rats, and these increased proteins in the telmisartan group were less than the vehicle and hydralazine group. Telmisartan administration resulted in significant suppression in tumor necrosis factor-α expression and nuclear factor-κB phosphorylation.

CONCLUSION:

Long-term telmisartan therapy may improve renal dysfunction, glomerulosclerosis, podocyte injury, and inflammation associated with EMT, TGF-β/Smad, MAPK, Rho-kinase pathway in SHRSP fatty rats. Thus, telmisartan may have significant therapeutic potential for metabolic syndrome.

• Authors: Fumihiro Sugiyama, Naohiko Kobayashi, Mayuko Ishikawa, Sho Onoda, Toshihiko Ishimitsu
• Journal: Clinical and experimental nephrology (Clin Exp Nephrol) Vol. 17 Issue 4 Pg. 515-24 (Aug 2013) ISSN: 1437-7799 [Electronic] Japan
• PMID: 23268284 (Publication Type: Journal Article)

Chemical References

• Benzimidazoles
• Benzoates
• Cell Cycle Proteins
• Desmin
• Smad4 Protein
• Transforming Growth Factor beta1
• Tumor Necrosis Factor-alpha
• Hydralazine
• Telmisartan

Topics

• Animals
• Benzimidazoles (therapeutic use)
• Benzoates (therapeutic use)
• Cell Cycle Proteins (biosynthesis)
• Desmin (biosynthesis)
• Epithelial-Mesenchymal Transition (drug effects)
• Hydralazine (therapeutic use)
• Kidney Diseases (prevention & control)
• Male
• Metabolic Syndrome (drug therapy)
• Nephritis (drug therapy, metabolism)
• Podocytes (drug effects, pathology)
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY
• Signal Transduction (drug effects)
• Smad4 Protein (physiology)
• Telmisartan
• Transforming Growth Factor beta1 (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)