Cytokine and Growth Factor Response in a Rat Model of Radiation Induced Injury to the Submental Muscles

Radiation-induced heart disease (RIHD) is a potential late side-effect of thoracic radiotherapy resulting in left ventricular hypertrophy (LVH) and fibrosis due to a complex pathomechanism leading to heart failure. Angiotensin-II receptor blockers (ARBs), including losartan, are frequently used to control heart failure of various etiologies. Preclinical evidence is lacking on the anti-remodeling effects of ARBs in RIHD, while the results of clinical studies are controversial. We aimed at investigating the effects of losartan in a rat model of RIHD. Male Sprague-Dawley rats were studied in three groups: (1) control, (2) radiotherapy (RT) only, (3) RT treated with losartan (per os 10 mg/kg/day), and were followed for 1, 3, or 15 weeks. At 15 weeks post-irradiation, losartan alleviated the echocardiographic and histological signs of LVH and fibrosis and reduced the overexpression of chymase, connective tissue growth factor, and transforming growth factor-beta in the myocardium measured by qPCR; likewise, the level of the SMAD2/3 protein determined by Western blot decreased. In both RT groups, the pro-survival phospho-AKT/AKT and the phospho-ERK1,2/ERK1,2 ratios were increased at week 15. The antiremodeling effects of losartan seem to be associated with the repression of chymase and several elements of the TGF-β/SMAD signaling pathway in our RIHD model.

Download Full-text

The reduction in insulin-like growth factor-1 and linear growth in a rat model of colitis is mediated by the combined inhibitory effects of interieukin-6 and usdernutrition

Gastroenterology ◽

10.1016/s0016-5085(01)81045-3 ◽

2001 ◽

Vol 120 (5) ◽

pp. A210-A210 ◽

Cited By ~ 1

Author(s):

A BALLINGER ◽

O AZOOZ ◽

M BAJAJELLIOTT ◽

M FARTHING

Keyword(s):

Growth Factor ◽

Rat Model ◽

Linear Growth ◽

Insulin Like Growth Factor ◽

Inhibitory Effects

Download Full-text

Mesenchymal Stem Cells Enhanced Cardiac Nerve Sprouting via Nerve Growth Factor in a Rat Model of Myocardial Infarction

Current Pharmaceutical Design ◽

10.2174/13816128113199990451 ◽

2014 ◽

Vol 20 (12) ◽

pp. 2023-2029 ◽

Cited By ~ 4

Author(s):

Jian Chen ◽

Shaoxin Zheng ◽

Hui Huang ◽

Suihua Huang ◽

Changqing Zhou ◽

...

Keyword(s):

Myocardial Infarction ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Nerve Growth Factor ◽

Growth Factor ◽

Rat Model ◽

Nerve Growth ◽

Cardiac Nerve ◽

Nerve Sprouting

Download Full-text

Engineered Stem Cells Improve Neurogenic Bladder by Overexpressing SDF-1 in a Pelvic Nerve Injury Rat Model

Cell Transplantation ◽

10.1177/0963689720902466 ◽

2020 ◽

Vol 29 ◽

pp. 096368972090246 ◽

Cited By ~ 2

Author(s):

Guan Qun Zhu ◽

Seung Hwan Jeon ◽

Kyu Won Lee ◽

Hyuk Jin Cho ◽

U-Syn Ha ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Growth Factor ◽

Neurogenic Bladder ◽

Rat Model ◽

Bladder Wall ◽

Bladder Function ◽

Pelvic Nerve ◽

Injured Nerve

There is still a lack of sufficient research on the mechanism behind neurogenic bladder (NB) treatment. The aim of this study was to explore the effect of overexpressed stromal cell-derived factor-1 (SDF-1) secreted by engineered immortalized mesenchymal stem cells (imMSCs) on the NB. In this study, primary bone marrow mesenchymal stem cells (BM-MSCs) were transfected into immortalized upregulated SDF-1-engineered BM-MSCs (imMSCs/eSDF-1+) or immortalized normal SDF-1-engineered BM-MSCs (imMSCs/eSDF-1−). NB rats induced by bilateral pelvic nerve (PN) transection were treated with imMSCs/eSDF-1+, imMSCs/eSDF-1−, or sham. After a 4-week treatment, the bladder function was assessed by cystometry and voiding pattern analysis. The PN and bladder tissues were evaluated via immunostaining and western blotting analysis. We found that imMSCs/eSDF-1+ expressed higher levels of SDF-1 in vitro and in vivo. The treatment of imMSCs/eSDF-1+ improved NB and evidently stimulated the recovery of bladder wall in NB rats. The recovery of injured nerve was more effective in the NB+imMSCs/eSDF-1+ group than in other groups. High SDF-1 expression improved the levels of vascular endothelial growth factor and basic fibroblast growth factor. Apoptosis was decreased after imMSCs injection, and was detected rarely in the NB+imMSCs/eSDF-1+ group. Injection of imMSCs boosted the expression of neuronal nitric oxide synthase, p-AKT, and p-ERK in the NB+imMSCs/eSDF-1+ group than in other groups. Our findings demonstrated that overexpression of SDF-1 induced additional MSC homing to the injured tissue, which improved the NB by accelerating the restoration of injured nerve in a rat model.

Download Full-text