GENE THERAPY FOR REDUCTION OF FIBROSIS IN A MODEL OF SPONTENOUSLY HYPERTENSIVE RATS

• Grant number: 12/00753-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2012
• End date: September 24, 2015
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Sang Won Han
• Grantee: Roberta Sessa Stilhano Yamaguchi
• Host Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 13/22527-0 - Gene therapy for reduction of fibrosis in a model of spontenously hypertensive rats, BE.EP.DR

Abstract

Fibrosis is a major acquired sequel after muscle injury. In more severe injuries, in which healing occurs slowly, fibrosis prevents the proper muscle contraction and can lead to chronic pain and muscle contractures. In addition to functional loss, scar tissue tends to suffer further injury due to the changing of nature of tissue. These events lead professional athletes to abandon their activities early. Injuries and muscle pain are also the main complaints of patients seen by orthopedist e general physician. Fibrosis is a process that is part of the tissue recovery and can be divided into the following steps: muscle injury, inflammation and muscle degeneration, muscle regeneration, fibrosis, and partial recovery of the injured muscle. Thus, fibrosis is a necessary step for recovery of damaged tissue, but when this process is exacerbated, as often occurs in cases of deeper lesions, leads to imperfect tissue regeneration. Hypertension may enhance fibrosis, and angiotensin II (AngII), which is primarily responsible for vasoconstriction, seems to trigger fibrosis signaling via TGF-beta1. One proof of this is the reduction of fibrosis by the use of losartan, an antagonist of AngII. The main objectives of this project are to study in detail the relationship of skeletal muscle fibrosis and hypertension via angiotensin receptor. In the second phase of the project, to develop a gene therapy protocol to treat muscle fibrosis.

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)

STILHANO, ROBERTA SESSA; SAMOTO, VIVIAN YOCHIKO; SILVA, LEONARDO MARTINS; PEREIRA, GUSTAVO JOSE; ERUSTES, ADOLFO GARCIA; SMAILI, SORAYA SOUBHI; HAN, SANG WON. Reduction in skeletal muscle fibrosis of spontaneously hypertensive rats after laceration by microRNA targeting angiotensin II receptor. PLoS One, v. 12, n. 10, OCT 23 2017. (12/00753-6, 15/20206-8)

MADRIGAL, JUSTIN L.; STILHANO, ROBERTA S.; SILTANEN, CHRISTIAN; TANAKA, KIMBERLY; REZVANI, SABAH N.; MORGAN, RYAN P.; REVZIN, ALEXANDER; HAN, SANG W.; SILVA, EDUARDO A.. Microfluidic generation of alginate microgels for the controlled delivery of lentivectors. JOURNAL OF MATERIALS CHEMISTRY B, v. 4, n. 43, p. 6989-6999, NOV 21 2016. (12/00753-6, 15/20206-8)