ライフサイエンスコーパス: SSc

1 SSc fibroblasts showed increased alpha-smooth muscle act

2 SSc lung fibroblasts remained growth factor dependent, d

3 SSc pathophysiology involves systemic inflammation and o

4 SSc was induced in BALB/c mice by daily s.c. injections

5 SSc-conditioned media inhibited EC tube formation, where

6 SSc-PAH patients showed significant thickening of Intima

7 l normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH).

8 ddition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several

9 n fibroblasts from 10 normal subjects and 10 SSc patients, showing increased expression in SSc fibrob

10 A total of 138 SSc patients with technically adequate echocardiograms w

11 s between these subset-specific genes and 30 SSc-associated polymorphic genes including STAT4, BLK, I

12 een SSc and periodontitis was examined in 58 SSc patients and 52 control patients, matched for age an

13 AR1 receptor antibody (anifrolumab) in adult SSc patients.

14 ere prospectively measured in IPAH (n=9) and SSc-PAH (n=15) patients at rest and during incremental a

15 case proteins are less abundant with age and SSc, and they exhibit an altered subcellular distributio

16 lar protein abundance phenotypes of aged and SSc cells.

17 we demonstrate similar behavior of aged and SSc skin fibroblasts in culture.

18 arin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early

19 ch induces collagen production by normal and SSc dermal fibroblasts.

20 o fibrotic responses in explanted normal and SSc fibroblasts and in 3D human skin equivalents, in par

21 ical oxygen species generation in normal and SSc fibroblasts.

22 onal effects of these agonists on normal and SSc fibroblasts.

23 TAR Abs predicted development of SSc-PAH and SSc-PAH-related mortality in a prospective analysis.

24 ed in SSc skin biopsy samples, and serum and SSc fibroblasts, and in fibrotic skin tissues from mice.

25 elation to IFN pathway activation status and SSc disease activity.

26 genesis of immune-mediated diseases, such as SSc.

27 The association between SSc and periodontitis was examined in 58 SSc patients an

28 ectasia, and a temporal association between SSc onset and RNA polymerase III antibodies.

29 dy indicates a possible relationship between SSc and periodontitis.

30 ferences observed in regional strain between SSc and control were unchanged after adjusting for RV sy

31 n contrast, Treg cells from skin affected by SSc produced significant amounts of IL-4 and IL-13.

32 the impaired angiogenesis that characterizes SSc.

33 Skin-resident and circulating SSc CD8(+)CD28(-) T cells produce high levels of the pro

34 Consequently, SSc patients may be complicated by erosive esophagitis a

35 In contrast, SSc samples had a mean score of 5.039 for R. glutinis (5

36 Patients with early, diffuse cutaneous SSc were enrolled in an open-label trial of fresolimumab

37 ial in which patients with diffuse cutaneous SSc were treated with C-82 or placebo on opposite forear

38 xposed to HOCl developed a diffuse cutaneous SSc with pulmonary fibrosis and anti-DNA topoisomerase 1

39 -1 expression and pantothenic acid determine SSc severity and can be used as markers of disease sever

40 in the skin of patients with early, diffuse SSc compared with that in normal controls.

41 ubjects and patients with limited or diffuse SSc.

42 Remarkably, patients with diffuse SSc also had increased expression of vanin-1 in skin and

43 in skin biopsies from patients with diffuse SSc.

44 glutinis may be present in the skin of early SSc patients at higher levels than in normal skin, raisi

45 Complementary studies examined SSc or control lung tissue and fibroblasts.

46 In contrast to healthy control fibroblasts, SSc fibroblasts proliferated in response to PDGFAA, wher

47 sents an attractive therapeutic approach for SSc.

48 umatism clinical classification criteria for SSc.

49 ts potential as a disease-modifying drug for SSc.

50 e of the main environmental risk factors for SSc.

51 with the apex was significantly greater for SSc than for controls (P<0.0001 for interaction).

52 ti-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations.

53 Outcome for SSc-PAH is poor compared with heritable or idiopathic fo

54 whether DMF is effective as a treatment for SSc dermal fibrosis.

55 y supports the use of DMF as a treatment for SSc dermal fibrosis.

56 RNA-seq was performed on four SSc patients and four controls, to a depth of 200 millio

57 cess in skin is phenotypically distinct from SSc, here we demonstrate similar behavior of aged and SS

58 migration of skin and lung fibroblasts from SSc patients and healthy controls.

59 Pathologic lung fibroblasts from SSc patients modify ECM during migration but remain grow

60 bserved in plasma and conditioned media from SSc patients.

61 Genetically, SSc is multi-factorial with many genetic risk loci for S

62 However, SSc-PAH patients receiving warfarin within the previous

63 hat EBV is able to persistently infect human SSc fibroblasts in vitro, inducing an aberrant innate im

64 -associated pulmonary arterial hypertension (SSc-PAH) is a rare disease characterized by a very disma

65 ng intrinsic subset assignment, may identify SSc patients whose MRSS will improve during MMF treatmen

66 In SSc-PAH patients, long-term warfarin was associated with

67 ough there have been many recent advances in SSc-pulmonary hypertension, further research is needed i

68 f IL-6Ralpha expression on ILC is altered in SSc.

69 and RNA processing decrease with age and in SSc, whereas those involved in mitochondrial and other m

70 VEGF did not induce angiogenesis in SSc ECs, but vitamin E or TXAR inhibition restored its e

71 nin-1 can open new therapeutic approaches in SSc.

72 e as predictive and prognostic biomarkers in SSc-PAH.

73 IPAH patients, but were markedly blunted in SSc-PAH.

74 ed fibroblasts are the key effector cells in SSc responsible for the excessive production of collagen

75 function of progenitor endothelial cells in SSc.

76 ties in regional and global contractility in SSc patients.

77 s, ventricular-vascular coupling declined in SSc-PAH.

78 lar calcium recycling, was also depressed in SSc-PAH (0.32+/-0.05 versus 0.50+/-0.05; P=0.039).

79 s that RV functional reserve is depressed in SSc-PAH patients.

80 RV contractile reserve is depressed in SSc-PAH versus IPAH subjects, associated with reduced ca

81 ssessment of gastrointestinal dysmotility in SSc.

82 n of TXAR, RhoA, and ROCK1/2 was elevated in SSc ECs.

83 Levels of tenascin-C are elevated in SSc skin biopsy samples, and serum and SSc fibroblasts,

84 Sc patients, showing increased expression in SSc fibroblasts.

85 Although the onset of fibrosis in SSc typically correlates with the production of autoanti

86 TGF-beta in the pathogenesis of fibrosis in SSc.

87 riggering the inflammatory response found in SSc.

88 le the esophageal involvement is frequent in SSc, no such motility disorder is seen in morphea.

89 Anti-AT1R and -ETAR Abs are more frequent in SSc-PAH/connective tissue disease-PAH compared with othe

90 have provided the MCID estimates for FVC% in SSc-ILD based changes at 12 months from baseline in two

91 ROCK activation were significantly higher in SSc ECs, whereas VEGF had no effect.

92 This ratio was higher in SSc without PH (Ees/Ea=2.3+/-1.2; P=0.02 versus SScPAH).

93 STAT3 signaling is hyperactivated in SSc in a TGFbeta-dependent manner.

94 lysine-modifying enzymes were identified in SSc but not control fibroblast extracellular matrix prep

95 umab and elucidate the role of type I IFN in SSc.

96 ic and end-diastolic RV volumes increased in SSc-PAH patients to offset contractile deficits, whereas

97 r the TXAR was activated by 8-isoprostane in SSc endothelial cells (ECs) and whether this pathway inh

98 nd has negative impact on quality of life in SSc.

99 Although fractional area change was lower in SSc patients than in controls (mean, 48.9 versus 55; P=0

100 to model pathogenic fibroblast migration in SSc in order to identify enhancing factors, measure the

101 leading cause of morbidity and mortality in SSc.

102 eduction in BMPRII expression is observed in SSc lung tissue and fibroblasts.

103 I, these mutations have not been observed in SSc-PAH.

104 stinal tract evaluation is justified only in SSc and not in morphea.

105 (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) i

106 The impact of MVECs perturbations in SSc goes beyond the initiation of the vascular disease t

107 in determining the profibrotic phenotype in SSc fibroblasts.

108 overexpression of multiple serum proteins in SSc patients, particularly those with an elevated baseli

109 ough which tissue fibrosis may be reduced in SSc patients.

110 ger treatment to promote fat regeneration in SSc skin.

111 -fibrotic CCN2 and proinflammatory S100A9 in SSc skin, and therefore contributes to the fibrosis and

112 Restoring adiponectin signaling in SSc patients therefore might represent an innovative pha

113 we sought to assess adiponectin signaling in SSc skin biopsies, and evaluate fibrosis in mice with ad

114 rogenous pattern of regional heart strain in SSc that is not detected by conventional measures of fun

115 pathy, autoimmunity, and oxidative stress in SSc.

116 ells represent a pathogenic T-cell subset in SSc and likely play a critical role in the early stage o

117 eaction and are epigenetically suppressed in SSc dermal fibroblasts, Friend leukaemia integration 1 (

118 gradation, may promote PAH susceptibility in SSc and provide a unifying mechanism across different fo

119 migration individually but showed synergy in SSc cells.

120 equent involvement of other organ systems in SSc patients with cardiac manifestations.

121 transforming growth factor-beta (TGFbeta) in SSc skin fibroblasts.

122 sion in skin may allow targeted treatment in SSc.

123 ogenous danger signal that is upregulated in SSc and drives TLR4-dependent fibroblast activation, and

124 However, these need to be validated in SSc for trials.

125 In a stepwise logistic regression, including SSc status, age, sex, education, smoking, alcohol consum

126 ion in mice with HOCl- and bleomycin-induced SSc.

127 c mice with hypochlorous acid (HOCl)-induced SSc by ELISA and Western blotting.

128 closamide in the mouse model of HOCl-induced SSc as well as the well-documented safety profile of thi

129 nn1 gene in vnn1(-/-) mice with HOCl-induced SSc prevented the development of characteristic features

130 In wild-type mice with HOCl-induced SSc, the vanin-1/pantetheinase pathway was dysregulated,

131 investigate, in a mouse model of ROS-induced SSc, the effects of niclosamide, an antihelmintic drug t

132 Hence, at the molecular level, SSc fibroblasts exhibit intrinsic characteristics of fib

133 Two new SSc-associated antibodies and their clinical association

134 red with 40 age- and sex-matched healthy non-SSc controls.

135 normalities were seen in 32 cases (68.1%) of SSc and none in morphea.

136 rtery thrombus formation was found in 19% of SSc-PAH patients.

137 ented abnormal reflux in 33 cases (80.5%) of SSc and no such abnormality in morphea.

138 symptoms were present in 39 cases (69.6%) of SSc which were mild in 22 (39.3%), moderate in 14 (25%),

139 esophagitis was seen in 17 cases (32.7%) of SSc and only two cases (7.14%) of morphea.

140 in, has been implicated in the activation of SSc fibroblasts.

141 nsic" gene expression subsets by analysis of SSc skin.

142 to the following: first, clinical aspects of SSc lung management, including classification, imaging,

143 ansion in studies of psychosocial aspects of SSc, and in the validation of psychosocial measures that

144 The strength of the association of SSc with AL remained statistically significant after add

145 The role and associations of SSc-associated antibodies for diagnosis and internal org

146 e, longitudinal pharmacodynamic biomarker of SSc skin disease decreased after fresolimumab treatment

147 and 31 newly and already diagnosed cases of SSc and morphea respectively were taken up for the study

148 esenchymal, endothelial, and immune cells of SSc patients may underlie the main pathological features

149 the fibrotic and inflammatory components of SSc and endothelial cell-specific Fli1-knockout mice rec

150 R and anti-ETAR Abs predicted development of SSc-PAH and SSc-PAH-related mortality in a prospective a

151 PAH is now a criterion for the diagnosis of SSc.

152 in greater insight into the epidemiology of SSc-pulmonary hypertension with regard to prevalence, in

153 y underlie the main pathological features of SSc including autoimmunity, vasculopathy, and fibrosis,

154 ously recapitulate all the three features of SSc, including fibrosis and vasculopathy of the skin and

155 US can be used to assess features of SSc, including synovitis, tenosynovitis, calcinosis, acr

156 The importance of SSc antibodies for diagnosis has become increasingly rec

157 enesis of gastrointestinal manifestations of SSc has expanded substantially in the last few decades.

158 in on the key pathological manifestations of SSc, including inflammation, vasculopathy, and tissue fi

159 gement of gastrointestinal manifestations of SSc.

160 drugs against the fibrotic manifestations of SSc.

161 ely inhibited proliferation and migration of SSc and healthy control fibroblasts and attenuated basal

162 The tight skin (Tsk)2/+ mouse model of SSc demonstrates signs similar to SSc including tight sk

163 h factor (TGF)-beta-dependent mouse model of SSc-PAH.

164 The pathogenesis of SSc and its progression are poorly understood.

165 ing the role of MVECs in the pathogenesis of SSc and the mechanisms for MVECs dysfunction in the dise

166 or epigenetic factors in the pathogenesis of SSc, and suggested defects in the function of progenitor

167 entral role for MVECs in the pathogenesis of SSc, and suggests further mechanisms for MVECs injury.

168 tion is a key element in the pathogenesis of SSc, but the initial triggers for MVEC dysfunction remai

169 elial cell antibodies in the pathogenesis of SSc, especially purified subsets of these antibodies lik

170 ay a significant role in the pathogenesis of SSc-associated interstitial lung disease.

171 role of inflammation in the pathogenesis of SSc-PAH.

172 like receptors (TLRs) in the pathogenesis of SSc.

173 ested this pathway in the pathophysiology of SSc.

174 oring were done in 52, 47 and 41 patients of SSc; and 28, 25 and 20 patients of morphea respectively.

175 d Fli1 mimicking the epigenetic phenotype of SSc skin spontaneously recapitulate all the three featur

176 isease state such as the risk or presence of SSc-ILD, the activity of lung involvement and the likeli

177 Despite FPR overexpression, the response of SSc fibroblasts to the same agonists was greatly reduced

178 at correlate negatively with the severity of SSc skin disease.

179 oblasts and endothelial cells in the skin of SSc patients, characterized by the expression of the EBV

180 increased in the blood and affected skin of SSc patients, independent of patient age, and correlates

181 N2 and other fibrotic markers in the skin of SSc patients.

182 y play a critical role in the early stage of SSc skin disease.

183 l information in assessing the ILD status of SSc patients.

184 could facilitate a refined stratification of SSc patients into clinically relevant subsets at the tim

185 The study of SSc is hindered by a lack of animal models that recapitu

186 ve received little attention in the study of SSc or fibrosis.

187 ity was significantly reduced in a subset of SSc skin biopsies.

188 andidate for molecular targeted therapies of SSc.

189 Transfer of SSc-IgG containing both autoantibodies into healthy C57B

190 ht be a viable strategy for the treatment of SSc.

191 ral event triggering the pathogenic triad of SSc.

192 that advance or change our understanding of SSc lung disease pathogenesis, thereby raising the poten

193 can contribute to a better understanding of SSc pathogenesis and identify novel biomarkers and thera

194 ances have been made in our understanding of SSc-associated lung disease, and this review attempts to

195 s have resulted in a better understanding of SSc-associated lung disease, the development of new in-v

196 cohol consumption, and body mass index, only SSc status, age, and sex remained significantly associat

197 h (CRF-GSEA) proved successful in predicting SSc patient ILD status with a high degree of success (>8

198 3, strongly suggesting that it might promote SSc fibrosis directly or indirectly by synergistically s

199 l-specific Fli1-knockout mice recapitulating SSc vasculopathy.

200 associations of several previously reported SSc risk loci were validated and further refined, and th

201 Scleroderma (SSc) is a complex and heterogeneous connective tissue di

202 e of morbidity and mortality in scleroderma (SSc).

203 ation of fibrotic diseases like scleroderma (SSc).

204 The pathogenesis of scleroderma (SSc) includes components of autoimmunity, vascular dysfu

205 olvement in systemic sclerosis (scleroderma [SSc]) adversely affects long-term prognosis, often remai

206 Systemic sclerosis (scleroderma, SSc) is a devastating fibrotic disease with few treatmen

207 gan system involved with systemic sclerosis (SSc) affecting approximately 90% of patients.

208 g the molecular basis of systemic sclerosis (SSc) and its various clinical manifestations.

209 the association between systemic sclerosis (SSc) and periodontitis.

210 istent organ fibrosis in systemic sclerosis (SSc) are not known but emerging evidence implicates toll

211 bute to skin fibrosis in systemic sclerosis (SSc) by affecting the differentiation of pluripotent der

212 In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Im

213 Systemic sclerosis (SSc) is a connective tissue disorder characterized by fi

214 Systemic sclerosis (SSc) is a generalized disorder of unknown etiology affec

215 Systemic sclerosis (SSc) is a multi-organ fibrotic disease with few treatmen

216 Systemic sclerosis (SSc) is a multisystem inflammatory and vascular disease

217 Systemic sclerosis (SSc) is a polygenic, autoimmune disorder of unknown etio

218 Systemic sclerosis (SSc) is a rare systemic autoimmune disease characterized

219 Systemic sclerosis (SSc) is a spreading fibrotic disease affecting the skin

220 Skin fibrosis in systemic sclerosis (SSc) is accompanied by attrition of dermal white adipose

221 Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis

222 Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis

223 Systemic sclerosis (SSc) is an autoimmune disorder characterized by fibrosis

224 Systemic sclerosis (SSc) is characterized by chronic inflammation and fibros

225 Systemic sclerosis (SSc) is manifested by fibrosis, vasculopathy and immune

226 of <2 mm in diameter in Systemic Sclerosis (SSc) patients with (n = 17) and without (n = 5) associat

227 s in the pathogenesis of systemic sclerosis (SSc), a connective tissue disorder characterized by auto

228 lood of individuals with systemic sclerosis (SSc), a disease characterized by fibrotic and vascular p

229 athogens as a trigger of systemic sclerosis (SSc), although neither a pathogen nor a mechanism of pat

230 ntifibrotic therapies in systemic sclerosis (SSc), and in parallel a rapid development in the identif

231 ibrosis is a hallmark of systemic sclerosis (SSc), and keratinocytes may be critical regulators of fi

232 long been implicated in systemic sclerosis (SSc), as expression of TGF-beta-regulated genes is incre

233 Systemic sclerosis (SSc), or scleroderma, is a heterogeneous and complex aut

234 in serologic testing for systemic sclerosis (SSc)-associated antibodies with respect to the diagnosis

235 n the pathophysiology of systemic sclerosis (SSc).

236 rotic disorders, such as systemic sclerosis (SSc).

237 t in the pathogenesis of systemic sclerosis (SSc).

238 rotic diseases including systemic sclerosis (SSc).

239 d in the pathogenesis of systemic sclerosis (SSc).

240 eading cause of death in systemic sclerosis (SSc).

241 l lung disease (ILD) - a systemic sclerosis (SSc, or scleroderma) clinical phenotype which is the lea

242 PAH associated with systemic sclerosis (SSc-PAH) has a substantially worse prognosis than idiopa

243 on (PAH) associated with systemic sclerosis (SSc-PAH).

244 psychosocial aspects of systemic sclerosis (SSc; scleroderma).

245 haracteristic feature of systemic sclerosis (SSc; scleroderma).

246 Given that SSc is a multifactorial disease caused by both genetic a

247 Multiplex profiling revealed that SSc epidermal explants release increased levels of CCN2

248 In addition, we show that SSc fibroblasts exhibit higher levels of senescence comp

249 sease and is time dependent, suggesting that SSc is a susceptibility factor.

250 The SSc intrinsic gene expression subsets (inflammatory, fib

251 nnaire is being increasingly accepted by the SSc experts as a validated instrument for evaluation of

252 We have characterized the SSc epidermis and asked whether SSc-injured epidermal ce

253 ase (-32.2% versus -23.3%; P=0.0001) for the SSc group.

254 For the SSc-LD group, 1- and 5-year survival was 83% and 76% com

255 l RNA (rRNA) of R. glutinis from each of the SSc samples.

256 Our results show that the SSc epidermis is hypertrophic, and has altered expressio

257 These data suggest that the SSc epidermis provides an important source of pro-fibrot

258 t the gene expression changes underlying the SSc subsets may be long-lived, but mechanistically inter

259 strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL

260 d activating AT1R and ETAR may contribute to SSc-PAH pathogenesis, and tested their functional and bi

261 Both antibodies may contribute to SSc-PAH via increased vascular endothelial reactivity an

262 of normal Treg cell function contributes to SSc is unknown.

263 te picture of the complex pathway leading to SSc disease pathogenesis.

264 e model of SSc demonstrates signs similar to SSc including tight skin and excessive deposition of der

265 At matched exercise (25 W), SSc-PAH patients did not augment contractility (end-syst

266 cterized the SSc epidermis and asked whether SSc-injured epidermal cells release factors capable of p

267 he number of known genetic associations with SSc, provided further insight into the pleiotropic effec

268 subsets and analyzed their connections with SSc-associated genetic polymorphisms.

269 cells in the blood and skin of patients with SSc acquired abnormal production of effector cytokines.

270 expression of this cytokine in patients with SSc and expression of the ST2 chain of the IL-33 recepto

271 heinase pathway in a cohort of patients with SSc and in controls.

272 ugh Treg cells in the blood of patients with SSc did not make TH2 cytokines, they contained a signifi

273 Adjusted for age and sex, patients with SSc had a 0.52 mm higher AL compared with controls (95%

274 Treg cells in the blood of patients with SSc had a normal phenotype and did not produce T-effecto

275 In unadjusted analyses, patients with SSc had a significant 0.61 mm higher AL (95% confidence

276 Patients with SSc in whom PH and significant interstitial lung disease

277 cytosol of CD8(+) T cells from patients with SSc reduces T-bet translocation into the nucleus and its

278 Patients with SSc undergoing lung transplantation have similar rates o

279 the blood and lesional skin of patients with SSc with severe skin thickening.

280 ia for lung transplantation in patients with SSc, discuss the implications and recommendations relate

281 duction by CD8(+) T cells from patients with SSc, focusing on T-bet modulation of GATA-3 activity, wh

282 us TLR activators in skin from patients with SSc, skin fibroblasts, and in mouse models of organ fibr

283 tudy demonstrates higher AL in patients with SSc, which remained significant after adjustment.

284 y higher and more prevalent in patients with SSc-PAH (n = 81) and connective tissue disease-associate

285 ound reduced BMPRII protein in patients with SSc-PAH and a relevant mouse model associated with incre

286 onal status in treatment-naive patients with SSc-PAH and may represent a very effective therapy for t

287 abel trial, 24 treatment-naive patients with SSc-PAH received ambrisentan 10 mg and tadalafil 40 mg d

288 he evaluation and screening of patients with SSc-PAH, and early detection has been shown to improve s

289 ont combination PAH therapy in patients with SSc-PAH.

290 n multiple clinical cohorts of patients with SSc.

291 ight contribute to fibrosis in patients with SSc.

292 eased in the skin and lungs of patients with SSc.

293 the leading cause of death of patients with SSc.

294 jects of various ages and from patients with SSc.

295 sis bed in seven (78%) of nine patients with SSc.

296 n in CD8(+)IL-13(+) cells from patients with SSc.

297 expressed in fibroblasts from patients with SSc.

298 dress the psychosocial needs of persons with SSc, interventions need to be developed and tested via r

299 Persons with SSc-LD appear to have similar survival and fBOS as perso

300 posttransplantation outcomes in persons with SSc-LD with esophageal involvement compared with persons