Potential adipokine involvement in systemic sclerosis
Potential adipokine involvement in systemic sclerosis
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脂肪因子可能参与系统性硬化症
DOI：
10.1136/ard.2010.129601b
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发表时间：
2010
影响因子：
27.4
通讯作者：
Neumann
中科院分区：
文献类型：
--
作者：
Frommer KW;Vasile M;Schmeiser T;Distler O;Riccieri V;Günther A;Roeb E;Müller-Ladner U;Neumann
方法收集例SSc患者（n=）和例健康对照者（n =）的食管胃镜活检标本（胃体、食管、胃窦）、肺组织（各n =）和皮肤活检标本（各n=）。脂联素和内脂素的定位通过免疫组织化学分析。通过ELISA测量健康对照（n= 1）和患有SSc（n = 1）、特发性肺纤维化（IPF）（n= 1）或EAA（n= 1）的患者的BAL中的脂肪因子水平。使用脂联素刺激的SSc皮肤成纤维细胞进行亲和素微阵列分析。分泌的白细胞介素6（IL-6）的SSc皮肤成纤维细胞，RA滑膜成纤维细胞（RASF）和骨关节炎SF（OASF）脂联素和内脂素刺激后进行了定量ELISA. ResultsAdipokines的表达在纤维化皮肤，纤维化肺组织和胃肠道的SSc患者相比，对照组增加。在SSc患者的GW中，脂肪因子定位于粘膜层内的非纤维化炎症部位。在细胞水平，脂肪因子主要由成纤维细胞（波形蛋白）、血管周围区域（CD 31）和炎性细胞浸润（CD 45）产生。脂肪因子在纤维化肺组织中强烈表达，并且在BAL中的水平在SSc中升高。亲和素阵列结果显示，趋化因子，促炎分子和基质金属蛋白酶的表达增加，细胞外基质和粘附分子的表达减少。在SSc皮肤成纤维细胞中，IL-6的分泌同样诱导脂联素和visfatin在RASF和OASF.ConclusionsOrgans参与SSc的病理表现出脂肪因子的表达增加。在体外实验中，SSc皮肤成纤维细胞与脂肪因子刺激导致增加的因子的表达，促进炎症和破坏细胞外基质，但减少纤维化因子的表达。这些发现表明脂肪因子在SSc中具有促炎症但抗纤维化作用。进一步研究脂肪因子的抗纤维化潜力可能揭示其参与SSc的病理生理机制，并为未来的治疗干预提供新的方法。
MethodsEsophagogastroscopy biopsy samples (corpus, oesophagus, antrum) were obtained from SSc patients (n= and healthy controls (n= as well as lung (n= each) and skin biopsy samples (n= each). Localisation of adiponectin and visfatin was analysed by immunohistochemistry. Adipokine levels were measured in BAL of healthy controls (n= and patients with SSc (n”), idiopathic pulmonary fibrosis (IPF)(n= or EAA (n= by ELISA. Affymetrix microarray analysis was performed using adiponectin-stimulated SSc skin fibroblasts. Secretion of interleukin 6 (IL-6) by SSc skin fibroblasts, RA synovial fibroblasts (RASF) and osteoarthritis SF (OASF) upon adiponectin and visfatin stimulation was quantified by ELISA.ResultsExpression of adipokines in fibrotic skin, fibrotic lung tissue and the GI tract of SSc patients was increased compared to controls. In the GW of SSc patients, adipokines were localised at non-fibrotic sites of inflammation within the mucosal layer. At the cellular level, adipokines are produced mainly by fibroblasts (vimentin), in the perivascular regions (CD31) and inflammatory cell infiltrates (CD45). Adipokines were strongly expressed in fibrotic lung tissue, and levels in BAL were elevated in SSc. Affymetrix array results showed an increase in expression of chemokines, pro-inflammatory molecules and matrix metalloproteinases, and a decrease in expression of extracellular matrix and adhesion molecules. In SSc skin fibroblasts, secretion of IL-6 was similarly induced by adiponectin and visfatin as in RASF and OASF.ConclusionsOrgans involved in the pathology of SSc showed increased expression of adipokines. In vitro experiments with SSc skin fibroblasts stimulated with adipokines resulted in increased expression of factors promoting inflammation and breaking down extracellular matrix but decreased expression of fibrogenic factors. These findings suggest a pro-inflammatory but anti-fibrotic effect of adipokines in SSc. Further investigations with focus on the anti-fibrotic potential of adipokines may reveal their involvement in the pathophysiological mechanisms of SSc and lead to new approaches for future therapeutic intervention.