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. 2020 Feb 28;40(2):BSR20191726.
doi: 10.1042/BSR20191726.

Transforming growth factor-β1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment

Jingjing Xie  1 , Bo Li  1 , Bing Yao  1 , Pingchao Zhang  1 , Lixin Wang  1 , Hua Lu  1 , Xuan Song  1
Affiliations

Transforming growth factor-β1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment

Jingjing Xie et al. Biosci Rep. .

Retraction in

Abstract

Background: During disc degeneration, inflammatory cytokine tumor necrosis factor (TNF)-α is correlated with nucleus pulposus (NP) cell apoptosis. Transforming growth factor (TGF)-β1 has the potential to regenerate degenerative disc.

Objective: To investigate the protective role of TGF-β1 against TNF-α-mediated NP cell apoptosis and the underlying mechanism.

Methods: Rat NP cells were treated with TNF-α (100 ng/ml) for 48 h. TGF-β1 was added into the culture medium to investigate its protective effects against TNF-α-induced NP cell apoptosis. Exogenous FasL was used to investigate the potential role of the Fas/FasL pathway in this process. Flow cytometry assay was used to analyze NP cell apoptosis. Real-time PCR and Western blotting were used to analyze gene and protein expression of apoptosis-related molecules.

Results: In TNF-α-treated NP cells, TGF-β1 significantly decreased NP cell apoptosis, declined caspase-3 and -8 activity, and decreased expression of Bax and caspase-3 (cleaved-caspase-3) but increased expression of Bcl-2. However, exogenous FasL partly reversed these effects of TGF-β1 in NP cells treated with TNF-α. Additionally, expression of Fas and FasL in TNF-α-treated NP cells partly decreased by TGF-β1, whereas exogenous FasL increased expression of Fas and FasL in NP cells treated with TGF-β1 and TNF-α.

Conclusion: TGF-β1 helps to inhibit TNF-α-induced NP cell apoptosis and the Fas/FasL pathway may be involved in this process. The present study suggests that TGF-β1 may be effective to retard inflammation-mediated disc degeneration.

Keywords: Fas/FasL; TGF-β1; TNF-α; apoptosis; nucleus pulposus.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

All animal experiments in the present study were performed in the Central Laboratory of Xinhua Hospital, and the animal tissue separation procedure was approved by the Ethics Committee at Xinhua Hospital affiliated to Medical School of Shanghai Jiaotong Universtiy [SHU(W) 2015-1202].

Figures

Figure 1
Figure 1. Flow cytometry analysis of NP cell apoptosis
(A) Representative images of flow cytometry analysis. (B) Histogram of apoptosis rate in different groups. Data are expressed as mean ± SD, n=3. *: Indicates a significant difference (P<0.05) between two groups.
Figure 2
Figure 2. Caspase-3 and caspase-8 activity measurement of NP cells
Data are expressed as mean ± SD, n=3. *: Indicates a significant difference (P<0.05) between two groups.
Figure 3
Figure 3. Gene expression of apoptosis-related molecules (Bcl-2, Bax and caspase-3) of NP cells
Data are expressed as mean ± SD, n=3. *: Indicates a significant difference (P<0.05) between two groups.
Figure 4
Figure 4. Protein expression of apoptosis-related molecules (Bcl-2, Bax and caspase-3) of NP cells
Data are expressed as mean ± SD, n=3. *: Indicates a significant difference (P<0.05) between two groups.
Figure 5
Figure 5. Protein expression of Fas and FasL of NP cells
Data are expressed as mean ± SD, n=3. *: Indicates a significant difference (P<0.05) between two groups.
See this image and copyright information in PMC

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