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September 2013 Volume 32 Issue 3

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Article

Smac/DIABLO regulates the apoptosis of hypertrophic scar fibroblasts

  • Authors:
    • Bao-Heng Liu
    • Liang Chen
    • Shi-Rong Li
    • Zhen-Xiang Wang
    • Wen-Guang Cheng
  • View Affiliations / Copyright

    Affiliations: Department of Plastic and Reconstructive Surgery, Southwest Hospital, The Third Military Medical University, Chongqing 400038, P.R. China
  • Pages: 615-622
    |
    Published online on: July 15, 2013
       https://doi.org/10.3892/ijmm.2013.1442
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Abstract

In abnormal skin wound healing, hypertrophic scars (HS) are characterized by excessive fibroblast hypercellularity and an overproduction of collagen, leading to atypical extracellular matrix (ECM) remodeling. Although the exact mechanisms of HS remain unclear, decreased HS fibroblast (HSFB) apoptosis and increased proliferation are evident in the development of HS. In this study, the contribution of the second mitochondria-derived activator of caspases/direct inhibitor of apoptosis protein (IAP)-binding protein with a low isoelectric point (pI) (Smac/DIABLO), an apoptosis-promoting protein released from the mitochondria, was investigated in human normal skin and HSFB cultures. The expression of Smac/DIABLO is usually decreased in many malignant tumors compared with normal tissues. Immunohistochemical analysis of skin tissues and the western blot analyses of fibroblasts revealed that the expression of Smac/DIABLO was lower in HS tissues compared with normal skin tissues. Of note, adenovirus-mediated Smac/DIABLO overexpression in the cultured HSFBs significantly reduced cell proliferation, as detected by the cell counting kit-8, and increased caspase-3 and -9 activity, as detected by spectrofluorimetry. In addition, it increased apoptosis, as detected by fluorescence-activated cell sorting (FACS). Furthermore, we found that the silencing of Smac with siRNA in the HSFBs induced a noticeable decrease in caspase-3 and -9 activity, leading to a significant reduction in apoptosis. In addition, the mRNA expression of type I and III pro-collagen detected in the HSFBs was significantly increased following the silencing of Smac with siRNA and was inhibited following Smac/DIABLO overexpression, as shown by real-time RT-PCR. In conclusion, Smac/DIABLO decreases the proliferation and increases the apoptosis of HSFBs. To our knowledge, the data from our study suggest for the first time that Smac/DIABLO is a novel therapeutic target for HS.
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Copy and paste a formatted citation
Spandidos Publications style
Liu B, Chen L, Li S, Wang Z and Cheng W: Smac/DIABLO regulates the apoptosis of hypertrophic scar fibroblasts . Int J Mol Med 32: 615-622, 2013.
APA
Liu, B., Chen, L., Li, S., Wang, Z., & Cheng, W. (2013). Smac/DIABLO regulates the apoptosis of hypertrophic scar fibroblasts . International Journal of Molecular Medicine, 32, 615-622. https://doi.org/10.3892/ijmm.2013.1442
MLA
Liu, B., Chen, L., Li, S., Wang, Z., Cheng, W."Smac/DIABLO regulates the apoptosis of hypertrophic scar fibroblasts ". International Journal of Molecular Medicine 32.3 (2013): 615-622.
Chicago
Liu, B., Chen, L., Li, S., Wang, Z., Cheng, W."Smac/DIABLO regulates the apoptosis of hypertrophic scar fibroblasts ". International Journal of Molecular Medicine 32, no. 3 (2013): 615-622. https://doi.org/10.3892/ijmm.2013.1442
Copy and paste a formatted citation
x
Spandidos Publications style
Liu B, Chen L, Li S, Wang Z and Cheng W: Smac/DIABLO regulates the apoptosis of hypertrophic scar fibroblasts . Int J Mol Med 32: 615-622, 2013.
APA
Liu, B., Chen, L., Li, S., Wang, Z., & Cheng, W. (2013). Smac/DIABLO regulates the apoptosis of hypertrophic scar fibroblasts . International Journal of Molecular Medicine, 32, 615-622. https://doi.org/10.3892/ijmm.2013.1442
MLA
Liu, B., Chen, L., Li, S., Wang, Z., Cheng, W."Smac/DIABLO regulates the apoptosis of hypertrophic scar fibroblasts ". International Journal of Molecular Medicine 32.3 (2013): 615-622.
Chicago
Liu, B., Chen, L., Li, S., Wang, Z., Cheng, W."Smac/DIABLO regulates the apoptosis of hypertrophic scar fibroblasts ". International Journal of Molecular Medicine 32, no. 3 (2013): 615-622. https://doi.org/10.3892/ijmm.2013.1442
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