Gene expression of transforming growth factor-β1 and hepatocyte growth factor during wound healing of injured rat vocal fold

2009 ◽  
Vol 119 (4) ◽  
pp. 806-810 ◽  
Author(s):  
Tsunehisa Ohno ◽  
Shigeru Hirano ◽  
Bernard Rousseau
2011 ◽  
Vol 301 (6) ◽  
pp. C1423-C1430 ◽  
Author(s):  
Kenjiro Honda ◽  
Koji Okamoto ◽  
Yasuhiro Mochida ◽  
Kunihiro Ishioka ◽  
Machiko Oka ◽  
...  

Maggot debridement therapy (MDT) is effective for treating intractable wounds, but its precise molecular mechanism, including the association between MDT and growth factors, remains unknown. We administered MDT to nine patients (66.3 ± 11.8 yr, 5 male and 4 female) with intractable wounds of lower extremities because they did not respond to conventional therapies. Significant increases of hepatocyte growth factor (HGF) levels were observed in femoral vein blood during 48 h of MDT ( P < 0.05), but no significant change was found for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-β1 (TGF-β1), or tumor necrosis factor-α (TNF-α). We conducted NIH-3T3 cell stimulation assay to evaluate the relation between HGF and protease activity in excretion/secretion (ES) derived from maggots. Compared with the control group, HGF was significantly higher in the 0.05 μg/ml ES group ( P < 0.01). Furthermore, protease inhibitors suppressed the increase of HGF ( P < 0.05). The HGF expression was increased in proportion to the ES protein concentration of 0.025 to 0.5 μg/ml. In fact, ES showed stronger capability of promoting HGF production and less cytotoxicity than chymotrypsin or bromelain. HGF is an important factor involved in cutaneous wound healing. Therefore, these results suggest that formation of healthy granulation tissue observed during MDT results from the increased HGF. Further investigation to identify molecules enhancing HGF expression by MDT will contribute greatly to drug target discovery for intractable wound healing therapy.


2009 ◽  
Vol 118 (8) ◽  
pp. 606-611 ◽  
Author(s):  
Yo Kishimoto ◽  
Shigeru Hirano ◽  
Atsushi Suehiro ◽  
Ichiro Tateya ◽  
Shin-Ichi Kanemaru ◽  
...  

Objectives We have previously demonstrated the therapeutic potential of hepatocyte growth factor (HGF) in the treatment of vocal fold scarring, although how exogenous HGF affects gene expression of endogenous HGF or extracellular matrix components in the vocal fold fibroblasts remains unclear. In this in vitro study, we aimed to clarify this aspect in order to better understand the effects of HGF on the vocal folds. Methods Fibroblasts were obtained from the lamina propria of the vocal folds of 5 Sprague-Dawley rats and were cultured with HGF at concentrations of 100, 10, 1, and 0 ng/mL. The cells were collected on days 1, 3, and 7, and the expression of endogenous HGF, its receptor c-Met, transforming growth factor-β1 (TGF-β1), procollagen types I and III, and hyaluronic acid synthase (HAS)-l and HAS-2 messenger RNAs (mRNAs) was examined by real-time reverse transcription-polymerase chain reaction. Results The expression of endogenous HGF and HAS-1 mRNAs increased significantly when exogenous HGF was administered at a concentration of 1 ng/mL. On day 1, the expression of TGF-β1 and HAS-2 mRNAs increased significantly in response to 1 ng/mL HGF. Conclusions Exogenous HGF triggered the up-regulation of endogenous HGF, TGF-β1, HAS-1, and HAS-2 mRNAs in vocal fold fibroblasts.


2002 ◽  
Vol 111 (8) ◽  
pp. 661-666 ◽  
Author(s):  
Shigeru Hirano ◽  
Susan Thibeault ◽  
Charles N. Ford ◽  
Diane M. Bless ◽  
Shin-Ichi Kanemaru

Vocal fold fibrotic scar is characterized by fibrosis of the lamina propria and epithelium, and is difficult to treat. Hepatocyte growth factor (HGF) has antifibrotic activity and has received attention as a possible therapeutic alternative to treat fibrosis. In this study, in order to clarify whether HGF can be involved in vocal fold scarring, we examined the existence of HGF and its receptor, c-Met, in rat vocal folds, and then the activity of HGF in rabbit injured vocal folds, using immunohistochemistry and enzyme-linked immunosorbent assay. We found HGF and c-Met on epithelial cells and gland cells of the rat vocal folds. On the injured vocal folds of rabbits, little HGF was observed immediately after injury, but prominent activity occurred simultaneously with reepithelialization of the vocal fold mucosa on days 10 to 15. The activity of HGF was observed on fibroblasts in the lamina propria, as well as the epithelium. It is suggested that HGF in the vocal folds is produced by the fibroblasts and delivered to the epithelium. The implication of these findings is that HGF is involved in wound healing of the vocal fold, and may provide an alternative approach in preventing and treating vocal fold scarring.


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