TGF-β1/Smad3 Signaling Pathway Mediates T-2 Toxin-Induced Decrease of Type II Collagen in Cultured Rat Chondrocytes
T-2 toxin can cause damage to the articular cartilage, but the molecular mechanism remains unclear. By employing the culture of rat chondrocytes, we investigated the effect of the TGF-β1/Smad3 signaling pathway on the damage to chondrocytes induced by T-2 toxin. It was found that T-2 toxin could red...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-11-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/9/11/359 |
| _version_ | 1811263031286431744 |
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| author | Yang Li Ning Zou Jing Wang Ke-Wei Wang Fu-Yuan Li Fu-Xun Chen Bing-Yu Sun Dian-Jun Sun |
| author_facet | Yang Li Ning Zou Jing Wang Ke-Wei Wang Fu-Yuan Li Fu-Xun Chen Bing-Yu Sun Dian-Jun Sun |
| author_sort | Yang Li |
| collection | DOAJ |
| description | T-2 toxin can cause damage to the articular cartilage, but the molecular mechanism remains unclear. By employing the culture of rat chondrocytes, we investigated the effect of the TGF-β1/Smad3 signaling pathway on the damage to chondrocytes induced by T-2 toxin. It was found that T-2 toxin could reduce cell viability and increased the number of apoptotic cells when compared with the control group. After the addition of the T-2 toxin, the production of type II collagen was reduced at mRNA and protein levels, while the levels of TGF-β1, Smad3, ALK5, and MMP13 were upregulated. The production of the P-Smad3 protein was also increased. Inhibitors of TGF-β1 and Smad3 were able to reverse the effect of the T-2 toxin on the protein level of above-mentioned signaling molecules. The T-2 toxin could promote the level of MMP13 via the stimulation of TGF-β1 signaling in chondrocytes, resulting in the downregulation of type II collagen and chondrocyte damage. Smad3 may be involved in the degradation of type II collagen, but the Smad3 has no connection with the regulation of MMP13 level. This study provides a new clue to elucidate the mechanism of T-2 toxin-induced chondrocyte damage. |
| first_indexed | 2024-04-12T19:37:37Z |
| format | Article |
| id | doaj.art-5f16ce0725304fa1966884b5af9abba2 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-12T19:37:37Z |
| publishDate | 2017-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-5f16ce0725304fa1966884b5af9abba22022-12-22T03:19:10ZengMDPI AGToxins2072-66512017-11-0191135910.3390/toxins9110359toxins9110359TGF-β1/Smad3 Signaling Pathway Mediates T-2 Toxin-Induced Decrease of Type II Collagen in Cultured Rat ChondrocytesYang Li0Ning Zou1Jing Wang2Ke-Wei Wang3Fu-Yuan Li4Fu-Xun Chen5Bing-Yu Sun6Dian-Jun Sun7Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention/ Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin Medical University, Harbin 150081, ChinaCenter for Endemic Disease Control, Chinese Center for Disease Control and Prevention/ Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin Medical University, Harbin 150081, ChinaCenter for Endemic Disease Control, Chinese Center for Disease Control and Prevention/ Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin Medical University, Harbin 150081, ChinaCenter for Endemic Disease Control, Chinese Center for Disease Control and Prevention/ Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin Medical University, Harbin 150081, ChinaCenter for Endemic Disease Control, Chinese Center for Disease Control and Prevention/ Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin Medical University, Harbin 150081, ChinaGaoqiao Community Health Service Center of Pudong New District, Shanghai 200137, ChinaCenter for Endemic Disease Control, Chinese Center for Disease Control and Prevention/ Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin Medical University, Harbin 150081, ChinaCenter for Endemic Disease Control, Chinese Center for Disease Control and Prevention/ Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin Medical University, Harbin 150081, ChinaT-2 toxin can cause damage to the articular cartilage, but the molecular mechanism remains unclear. By employing the culture of rat chondrocytes, we investigated the effect of the TGF-β1/Smad3 signaling pathway on the damage to chondrocytes induced by T-2 toxin. It was found that T-2 toxin could reduce cell viability and increased the number of apoptotic cells when compared with the control group. After the addition of the T-2 toxin, the production of type II collagen was reduced at mRNA and protein levels, while the levels of TGF-β1, Smad3, ALK5, and MMP13 were upregulated. The production of the P-Smad3 protein was also increased. Inhibitors of TGF-β1 and Smad3 were able to reverse the effect of the T-2 toxin on the protein level of above-mentioned signaling molecules. The T-2 toxin could promote the level of MMP13 via the stimulation of TGF-β1 signaling in chondrocytes, resulting in the downregulation of type II collagen and chondrocyte damage. Smad3 may be involved in the degradation of type II collagen, but the Smad3 has no connection with the regulation of MMP13 level. This study provides a new clue to elucidate the mechanism of T-2 toxin-induced chondrocyte damage.https://www.mdpi.com/2072-6651/9/11/359T-2 toxinchondrocytesTGF-β1Smad3type II collagen |
| spellingShingle | Yang Li Ning Zou Jing Wang Ke-Wei Wang Fu-Yuan Li Fu-Xun Chen Bing-Yu Sun Dian-Jun Sun TGF-β1/Smad3 Signaling Pathway Mediates T-2 Toxin-Induced Decrease of Type II Collagen in Cultured Rat Chondrocytes Toxins T-2 toxin chondrocytes TGF-β1 Smad3 type II collagen |
| title | TGF-β1/Smad3 Signaling Pathway Mediates T-2 Toxin-Induced Decrease of Type II Collagen in Cultured Rat Chondrocytes |
| title_full | TGF-β1/Smad3 Signaling Pathway Mediates T-2 Toxin-Induced Decrease of Type II Collagen in Cultured Rat Chondrocytes |
| title_fullStr | TGF-β1/Smad3 Signaling Pathway Mediates T-2 Toxin-Induced Decrease of Type II Collagen in Cultured Rat Chondrocytes |
| title_full_unstemmed | TGF-β1/Smad3 Signaling Pathway Mediates T-2 Toxin-Induced Decrease of Type II Collagen in Cultured Rat Chondrocytes |
| title_short | TGF-β1/Smad3 Signaling Pathway Mediates T-2 Toxin-Induced Decrease of Type II Collagen in Cultured Rat Chondrocytes |
| title_sort | tgf β1 smad3 signaling pathway mediates t 2 toxin induced decrease of type ii collagen in cultured rat chondrocytes |
| topic | T-2 toxin chondrocytes TGF-β1 Smad3 type II collagen |
| url | https://www.mdpi.com/2072-6651/9/11/359 |
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