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Action mechanism of the anti-inflammatory galectin 1 protein in renal injury induced by the ischemia and reperfusion process: in vivo and in vitro analyses

Grant number: 11/22113-6
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): January 01, 2012
Effective date (End): December 31, 2013
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Sonia Maria Oliani
Grantee:Carla Patrícia Carlos
Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Introduction: During the procedures involved in organ transplantation, there is the condition of ischemia and reperfusion (IR), which is one of the causes of impaired acute renal graft. Despite advances in the field, mortality due to acute renal failure is high. The ischemic process itself is very harmful, but reperfusion can lead to a series of complications that may increase tissue damage and, associated with systemic complications, endanger the lives of patients. Objective: the aim of the present study is to analyze, in vivo and in vitro, the expression and the action mechanism of endogenous protein galectin-1 (Gal-1) in the kidney and renal tubular epithelial cells under normal conditions and after injury caused by the IR process. Methods: For in vivo experiments, male Wistar rats, weighing 200-220 g, will be distributed in four groups (8 rats / group) sacrificed 48 hours after the IR procedure, as follows: SHAM (IR surgery without clamping + saline), IR (IR + saline), IR + GAL-1 (100 mg Gal-1 30 min before IR), IR + DEX (100 mg dexamethasone 30 min before IR). The following parameters will be assessed: renal function by quantifying microalbuminuria and creatinine clearance; renal injury by histopathological analysis of acute tubular necrosis and the influx of neutrophils; renal injury by analysis of the influx of macrophages by immunohistochemistry; urinary evaluation of KIM-1 (molecule 1 of proximal tubular injury, a marker for proximal tubular injury and acute kidney injury); pro-inflammatory cytokines/chemokines (IL-1B, IL-6, TNF-alpha and MCP-1) and anti-inflammatory (IL-4 and IL-10) by MAGPIX system; expression of endogenous Gal-1 by immunohistochemistry; expression of adhesion molecules ²2 integrin and L-selectin in blood leukocytes by flow cytometry; immunohistochemistry to intercellular adhesion molecule ICAM-1, which is expressed in the kidney, and interacts with the leukocyte ²2 integrin during cell migration. For in vitro studies, we will evaluate the anti-inflammatory effects of the administration of hrGal-1 in human renal proximal tubular cells (HK-2 strain), compared with the effect of dexamethasone in periods 0, 2, 8, 16 and 24 hours after hypoxia-reoxygenation, checking the following aspects: Gal-1 expression by Western blotting; expression of ICAM-1 by immunofluorescence; evaluation of the marker KIM-1, pro-inflammatory cytokines/chemokines (IL-1B, IL-6, TNF-alpha and MCP-1) and anti-inflammatory (IL-4 and IL-10) by MAGPIX system, obtained in the supernatants of cell cultures. With these considerations, we propose that this study will not only make it possible to understand the mechanisms involved in the pathogenesis of IR injury, but also the molecules that can modulate the process, and can be assessed as potential therapeutic agents in the control of a lesion.

Articles published in Agência FAPESP about the scholarship:
Potential therapeutic target for acute kidney failure is discovered 

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CARLOS, CARLA P.; SILVA, ANALICE A.; GIL, CRISTIANE D.; OLIANI, SONIA M. Pharmacological treatment with galectin-1 protects against renal ischaemia-reperfusion injury. SCIENTIFIC REPORTS, v. 8, JUN 22 2018. Web of Science Citations: 1.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.
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