Abstract
BackgroundFibrosis is a major contributor to systemic sclerosis (SSc)-related morbidity, and rapid, progressive skin involvement predicts later mortality. Western medicine therapies for SSc cannot produce satisfactory effects currently, while Traditional Chinese Medicine (TCM), such as the Wenyang Huazhuo Tongluo (WYHZTL) formula, a Chinese herbal decoction, has shown amazing anti-fibrosis efficacy on SSc in clinical applications. This study is aiming to investigate the anti-fibrotic mechanism of WYHZTL formula for the treatment of SSc.MethodsFibroblasts from primary culture of skin lesions of SSc patients were exposed to rat medicated sera containing WYHZTL or XAV939, a small-molecule inhibitor of both tankyrase 1/2 and Wnt/β-catenin pathway. Cell counting kit-8 assay and Annexin V FITC/PI apoptosis kit were used to analyze cell proliferation and apoptosis in fibroblasts, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to detect the mRNA and protein levels of cyclin D1 and survivin.ResultsAfter 28, 48 and 72 h of incubation, the proliferative ability of the fibroblasts cells was obviously reduced by the sera containing WYHZTL compared with that in the control group; the percentage of apoptotic cell population in the sera containing WYHZTL treated fibroblasts cells was significantly higher than that in those treated with the control sera, and was about similar to that in those treated with XAV939. The sera containing WYHZTL could down-regulate both mRNA and protein levels of cyclin D1 and survivin, compared with the control group.ConclusionsThe present study demonstrates the antiproliferative and pro-apoptotic actions of WYHZTL formula against fibroblasts and the effect may be related to the down-regulation of mRNA and protein levels of cyclin D1 and survivin in SSc.
Highlights
Fibrosis is a major contributor to systemic sclerosis (SSc)-related morbidity, and rapid, progressive skin involvement predicts later mortality
Effect of rat medicated sera containing Wenyang Huazhuo Tongluo (WYHZTL) on proliferation of fibroblasts In order to confirm the role of WYHZTL formula in the proliferation of fibroblasts, the rat medicated sera containing WYHZTL were added into the primary culture fibroblasts
The percentage of late apoptotic cell population in the sera containing WYHZTL treated cells was clearly higher than that in those treated with the control sera and was slightly lower than that in those treated with XAV939 (P < 0.01)
Summary
Fibrosis is a major contributor to systemic sclerosis (SSc)-related morbidity, and rapid, progressive skin involvement predicts later mortality. Western medicine therapies for SSc cannot produce satisfactory effects currently, while Traditional Chinese Medicine (TCM), such as the Wenyang Huazhuo Tongluo (WYHZTL) formula, a Chinese herbal decoction, has shown amazing anti-fibrosis efficacy on SSc in clinical applications. This study is aiming to investigate the anti-fibrotic mechanism of WYHZTL formula for the treatment of SSc. Systemic sclerosis (SSc) is an autoimmune and/or autoinflammatory disease mainly characterized by the excessive accumulation of extracellular matrix (ECM), especially as collagen, and by extensive fibrosis in skin and eventually in multiple internal organs, such as lung, heart, esophagus and kidney [1]. Vascular damage, abnormal metabolism of connective tissue and a complex interaction of them are thought to be involved in SSc. Fibrosis is a major contributor to the disease related morbidity, and rapid, progressive skin involvement predicts later mortality [2]. The clinical effects of these therapies are of questionable significance currently, such as methotrexate and cyclophosphamide [3, 4]
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