Apoptosis Modulation as a Promising Target for Treatment of Systemic Sclerosis

Chabaud, Stéphane; Moulin, Véronique J.

doi:10.1155/2011/495792

Cited by 10 publications

(12 citation statements)

References 159 publications

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“…In addition, activating apoptotic pathways is an important strategy for treating intractable diseases such as cancer and autoimmunity, whereas limiting apoptosis may be beneficial for treating liver and heart failure and neurodegenerative diseases (Fischer and Schulze-Osthoff, 2005; Narula et al ., 2006; Guicciardi and Gores, 2010; Chabaud and Moulin, 2011). …”

Section: Introductionmentioning

confidence: 99%

Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response

Tang

Mak

et al. 2012

MBoC

236

288

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Section: Introductionmentioning

confidence: 99%

Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response

Tang

Mak

et al. 2012

MBoC

236

288

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“…It’s known that the cell cycle transition from the G1 to S phase is regulated by cyclin D1, and cyclin D1 activation promotes the passage of cells through the G1 restriction checkpoint [ 12 , 13 ]. Apoptosis is a key mechanism involved in fibrosis of SSc [ 14 ], and survivin is an inhibitor of apoptotic protein gene family and a cell cycle regulator, it is critically required for suppression of apoptosis and ensuring normal cell division in the G2/M phase of the cell cycle [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Wenyang Huazhuo Tongluo formula, a Chinese herbal decoction, improves skin fibrosis by promoting apoptosis and inhibiting proliferation through down-regulation of survivin and cyclin D1 in systemic sclerosis

Han¹,

Bian²,

Ouyang³

et al. 2016

BMC Complement Altern Med

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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.

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“…e development of dcSSc may be induced by cell cycle arrest, activation of DNA repair mechanisms, and inactivation of the apoptosis pathway [26]. It is known that the inhibition of apoptosis is a key mechanism of fibrosis [27]. In the present study, the relationship between PR and PP genotypes of the TP53 gene and dcSSc susceptibility was observed.…”

Section: Discussionmentioning

confidence: 49%

NOTCH3 T6746C and TP53 P72R Polymorphisms Are Associated with the Susceptibility to Diffuse Cutaneous Systemic Sclerosis

Zmorzyński

Wojcierowska-Litwin

Kowal

et al. 2020

BioMed Research International

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Introduction. NOTCH pathway and TP53 protein are involved in the development of fibrosis and autoimmune disorders, respectively. The aim of this study was to evaluate the role of single nucleotide polymorphisms (SNPs) of NOTCH3 and TP53 genes and serum anti-TP53 antibodies with the susceptibility, clinical subset of systemic sclerosis (SSc), and clinical profile of SSc patient, particularly with lung involvement and disease activity. Objects and Methods. 124 white Polish SSc patients (101 with limited cutaneous SSc–lcSSc, and 23 with diffuse cutaneous SSc–dcSSc) and 100 healthy individuals were included in the study. Patients were assessed for the presence of autoantibodies and interstitial lung disease. Two SNPs at position 6746 of NOTCH3 gene (C/T alleles) and 215 of the TP53 gene (P/R alleles) were genotyped by PCR-restriction fragment length polymorphism. Serum levels of anti-TP53 antibodies were analyzed by means of ELISA. Results. The genotypic frequencies of the NOTCH3 gene for SSc patients diverged significantly from Hardy–Weinberg equilibrium (p=0.03; χ2 = 4.63). There was no significant difference between SSc patients and the control population in allele frequencies of both SNPs. The CT + CC genotypes of NOTCH3 influenced the susceptibility to SSc (OR = 1.85, p=0.04), including dcSSc (OR = 3.43, p=0.04), and active form of SSc (OR = 5.46, p<0.001). The PR + RR genotypes of the TP53 gene were associated only with dcSSc susceptibility (OR = 3.30, p=0.034). The levels of anti-TP53 antibodies were not related to studied SNPs and clinical parameters of SSc including the presence of specific antibodies and interstitial lung disease. Conclusion. The CT + CC genotypes of NOTCH3 gene and PR + RR genotypes of the TP53 gene increased the risk of dcSSc development. Moreover, genotypes of CT + CC were associated with the active form of SSc suggesting the role of the NOTCH pathway in the pathogenesis of this disease.

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Apoptosis Modulation as a Promising Target for Treatment of Systemic Sclerosis

Cited by 10 publications

References 159 publications

Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response

Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response

Wenyang Huazhuo Tongluo formula, a Chinese herbal decoction, improves skin fibrosis by promoting apoptosis and inhibiting proliferation through down-regulation of survivin and cyclin D1 in systemic sclerosis

NOTCH3 T6746C and TP53 P72R Polymorphisms Are Associated with the Susceptibility to Diffuse Cutaneous Systemic Sclerosis

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