Induction of TIMP-1 and HSP47 synthesis in primary keloid fibroblasts by exogenous nitric oxide

Hsu, Yi-Chiang; Wang, Leng-Fang; Chien, Yie W.; Lee, Woan-Ruoh

doi:10.1016/j.jdermsci.2006.10.002

« Previous Next »Journal of Dermatological Science
Volume 45, Issue 1 , Pages 37-44, January 2007

Induction of TIMP-1 and HSP47 synthesis in primary keloid fibroblasts by exogenous nitric oxide

Yi-Chiang Hsu
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
- InnovaTherapeutics Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Corresponding authors at: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei and Innova Therapeutics Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. Tel.: +886 7 313 7920; fax: +886 7 313 5986.
Leng-Fang Wang
- Department of Biochemistry, College of Medicine, Taipei Medical University, Taipei, Taiwan
Yie W. Chien
- InnovaTherapeutics Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
Woan-Ruoh Lee
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Department of Dermatology, Taipei Medical University Hospital, Taipei, Taiwan
- Corresponding authors at: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei and Innova Therapeutics Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. Tel.: +886 7 313 7920; fax: +886 7 313 5986.

Received 22 July 2006; received in revised form 3 October 2006; accepted 4 October 2006.

Summary

Background

The excessive accumulation of extracellular matrix is a hallmark of many fibrotic diseases, including the hypertrophic scar and keloid. Recent reports from this research team had shown that exogenous nitric oxide (NO) participates in the keloid formation; however, its role on the synthesis of fibrotic factor (TGF-β1, TIMP-1 and HSP47) in the keloid fibroblasts (KF) remained unclear.

Objective

In this study, to better define the potential effect of exogenous NO on the expression of fibrotic factors in KF, the enhancing effect of exogenous NO, released from a NO donor, on the synthesis of fibrotic factors in KF was investigated.

Methods

The seven primary KF cultures were set up to measure the effect of exogenous NO on enhancing the expression of fibrotic factor.

Results

Elevation of cellular cGMP levels was observed to be induced by NO or blocked by the hydrolysis activity of phosphodiesterase (PDE) by the PDE inhibitor. The elevated levels of cellular cGMP were noted to enhance the expression of TIMP-1 and HSP47 in KF. Exogenous NO was found to significantly accelerate the production of TIMP-1 and HSP47 in the seven primary KFs with a corresponding increase in the production of TGF-β1.

Conclusion

The results have led to a conclusion, that is: the excess collagen formations in the keloid lesion may be attributed to the NO/cGMP signal pathway by initiating a rapid increase in the expression of TGF-β1, TIMP-1 and HSP47 in the KF cells.

Keywords: Nitric oxide (NO), Heat shock protein 47 (HSP47), Tissue inhibitor of MMP (TIMP)-1