Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice
OBJECTIVE: To investigate the antifibrotic effects of crocetin in scleroderma fibroblasts and in sclerotic mice. METHODS: Skin fibroblasts that were isolated from three systemic scleroderma (SSc) patients and three healthy subjects were treated with crocetin (0.1, 1 or 10 μM). Cell proliferation w...
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| Format: | Article |
| Language: | English |
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Elsevier España
2013-10-01
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| Series: | Clinics |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322013001001350&lng=en&tlng=en |
| _version_ | 1811327599360606208 |
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| author | Yinghua Song Lubing Zhu Ming Li |
| author_facet | Yinghua Song Lubing Zhu Ming Li |
| author_sort | Yinghua Song |
| collection | DOAJ |
| description | OBJECTIVE: To investigate the antifibrotic effects of crocetin in scleroderma fibroblasts and in sclerotic mice. METHODS: Skin fibroblasts that were isolated from three systemic scleroderma (SSc) patients and three healthy subjects were treated with crocetin (0.1, 1 or 10 μM). Cell proliferation was measured with an MTT assay. Alpha-smooth muscle actin was detected via an immunohistochemical method. Alpha 1 (I) procollagen (COL1A1), alpha 1 (III) procollagen (COL3A1), matrix metalloproteinase (MMP)-1 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA levels were measured using real-time PCR. SSc mice were established by the subcutaneous injection of bleomycin. Crocetin (50 mg/kg/d) was injected intraperitoneally for 14 days. Dermal thickness and lung fibrosis were assessed with Masson's trichrome staining. Plasma ET-1 was detected with an enzyme-linked immunosorbent assay (ELISA). Skin and lung ET-1 and COL1A1 mRNA levels were measured via real-time PCR. RESULTS: Crocetin inhibited the proliferation of SSc and normal fibroblasts, an effect that increased with crocetin concentration and incubation time. Crocetin decreased the expression of α-SMA and the levels of mRNA for COL1A1, COL3A1 and matrix metalloproteinase-1, while crocetin increased TIMP-1 mRNA levels in both SSc and normal fibroblasts. Skin and lung fibrosis was induced, and the levels of ET-1 in the plasma, skin and lungs were elevated in bleomycin-injected mice. Crocetin alleviated the thickening of the dermis and lung fibrosis; decreased COL1A1 mRNA levels in the skin and lung; and simultaneously decreased ET-1 concentrations in the plasma and ET-1 mRNA levels in the skin and lungs of the bleomycin-induced sclerotic mice, especially during the early phase (weeks 1-3). CONCLUSION: Crocetin inhibits cell proliferation, differentiation and collagen production in SSc fibroblasts. Crocetin alleviates skin and lung fibrosis in a bleomycin-induced SSc mouse model, in part due to a reduction in ET-1. |
| first_indexed | 2024-04-13T15:09:38Z |
| format | Article |
| id | doaj.art-1438bba37e1e46a0ac1d501eb3057c49 |
| institution | Directory Open Access Journal |
| issn | 1980-5322 |
| language | English |
| last_indexed | 2024-04-13T15:09:38Z |
| publishDate | 2013-10-01 |
| publisher | Elsevier España |
| record_format | Article |
| series | Clinics |
| spelling | doaj.art-1438bba37e1e46a0ac1d501eb3057c492022-12-22T02:42:02ZengElsevier EspañaClinics1980-53222013-10-0168101350135710.6061/clinics/2013(10)10S1807-59322013001001350Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic miceYinghua SongLubing ZhuMing LiOBJECTIVE: To investigate the antifibrotic effects of crocetin in scleroderma fibroblasts and in sclerotic mice. METHODS: Skin fibroblasts that were isolated from three systemic scleroderma (SSc) patients and three healthy subjects were treated with crocetin (0.1, 1 or 10 μM). Cell proliferation was measured with an MTT assay. Alpha-smooth muscle actin was detected via an immunohistochemical method. Alpha 1 (I) procollagen (COL1A1), alpha 1 (III) procollagen (COL3A1), matrix metalloproteinase (MMP)-1 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 mRNA levels were measured using real-time PCR. SSc mice were established by the subcutaneous injection of bleomycin. Crocetin (50 mg/kg/d) was injected intraperitoneally for 14 days. Dermal thickness and lung fibrosis were assessed with Masson's trichrome staining. Plasma ET-1 was detected with an enzyme-linked immunosorbent assay (ELISA). Skin and lung ET-1 and COL1A1 mRNA levels were measured via real-time PCR. RESULTS: Crocetin inhibited the proliferation of SSc and normal fibroblasts, an effect that increased with crocetin concentration and incubation time. Crocetin decreased the expression of α-SMA and the levels of mRNA for COL1A1, COL3A1 and matrix metalloproteinase-1, while crocetin increased TIMP-1 mRNA levels in both SSc and normal fibroblasts. Skin and lung fibrosis was induced, and the levels of ET-1 in the plasma, skin and lungs were elevated in bleomycin-injected mice. Crocetin alleviated the thickening of the dermis and lung fibrosis; decreased COL1A1 mRNA levels in the skin and lung; and simultaneously decreased ET-1 concentrations in the plasma and ET-1 mRNA levels in the skin and lungs of the bleomycin-induced sclerotic mice, especially during the early phase (weeks 1-3). CONCLUSION: Crocetin inhibits cell proliferation, differentiation and collagen production in SSc fibroblasts. Crocetin alleviates skin and lung fibrosis in a bleomycin-induced SSc mouse model, in part due to a reduction in ET-1.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322013001001350&lng=en&tlng=enCrocetinFibroblastsSystemic sclerodermaCollagenFibrosis |
| spellingShingle | Yinghua Song Lubing Zhu Ming Li Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice Clinics Crocetin Fibroblasts Systemic scleroderma Collagen Fibrosis |
| title | Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice |
| title_full | Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice |
| title_fullStr | Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice |
| title_full_unstemmed | Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice |
| title_short | Antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin-induced sclerotic mice |
| title_sort | antifibrotic effects of crocetin in scleroderma fibroblasts and in bleomycin induced sclerotic mice |
| topic | Crocetin Fibroblasts Systemic scleroderma Collagen Fibrosis |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322013001001350&lng=en&tlng=en |
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