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(Reference retrieved automatically from Google Scholar through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Induction of Heme Oxygenase-1 Can Halt and Even Reverse Renal Tubule-Interstitial Fibrosis

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Author(s):
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Correa-Costa, Matheus [1, 2] ; Semedo, Patricia [2] ; Monteiro, Ana Paula F. S. [2] ; Silva, Reinaldo C. [2] ; Pereira, Rafael L. [2] ; Goncalves, Giselle M. [1] ; Marcusso Marques, Georgia Daniela [2] ; Cenedeze, Marcos A. [2] ; Faleiros, Ana C. G. [3] ; Keller, Alexandre C. [2] ; Shimizu, Maria H. M. [4] ; Seguro, Antonio C. [4] ; Reis, Marlene A. [3] ; Pacheco-Silva, Alvaro [2] ; Camara, Niels O. S. [1, 2]
Total Authors: 15
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Div Nephrol, Lab Clin & Expt Immunol, Sao Paulo - Brazil
[3] Univ Fed Triangulo Mineiro, Div Pathol, Uberaba - Brazil
[4] Univ Sao Paulo, Sch Med, Dept Nephrol, Sao Paulo - Brazil
Total Affiliations: 4
Document type: Journal article
Source: PLoS One; v. 5, n. 12, p. e14298, 2010.
Web of Science Citations: 48
Abstract

Background: The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed. Aim: We explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease. Methods: Sprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO) and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed. Results: Pre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-beta protein production was significantly lower in Hemin-treated animals. Conclusion: Treatment with Hemin was able both to prevent the progression of fibrosis and to reverse an established renal scar. Modulation of inflammation appears to be the major mechanism behind HO-1 cytoprotection. (AU)

FAPESP's process: 07/07139-3 - The role of heme oxygenase 1 in different renal inflammatory process in experimental animal models
Grantee:Niels Olsen Saraiva Câmara
Support Opportunities: Research Projects - Thematic Grants