MMPs-2 and -14 Are Elevated in Eosinophilic Esophagitis and Reduced Following Topical Corticosteroid Therapy.
MMPs-2 and -14 Are Elevated in Eosinophilic Esophagitis and Reduced Following Topical Corticosteroid Therapy.
复制标题
DOI：
10.1097/mpg.0000000000000668
复制
发表时间：
2015-08
影响因子：
2.9
通讯作者：
Aceves SS
中科院分区：
文献类型：
--
作者：
Beppu L;Yang T;Luk M;Newbury RO;Palmquist J;Dohil R;Kurten RC;Broide DH;Aceves SS
嗜酸性粒细胞性食管炎（EoE）是一种慢性抗原介导的疾病，发生于儿童和成人，伴有食管重构和纤维化。重塑相关基质金属蛋白酶（MMPs）的表达在EoE中尚未详细报道。采用qPCR和免疫组织化学/免疫荧光技术，在EoE成纤维细胞、活跃和不活跃的儿科EoE活检和非病变对照活检中评估MMP-2和-14的表达和细胞定位。分析tgf - β1对培养食管上皮（HET1A）细胞MMP-2表达的影响。在EoE成纤维细胞和活检组织中表达MMP-2和-14 mRNA。增生上皮细胞在EoE中比对照组更丰富地产生MMP-14 (p<0.001)，上皮细胞MMP-14的表达程度与基底带增生呈正相关（r=0.65, p=0.002）。EoE固有层MMP-2和-14阳性细胞数（906±167和701±93细胞/mm2）高于对照组（258±93 p<0.01和232±54细胞/mm2 p<0.01）， MMP-14表达与纤维化严重程度相关。外用皮质类固醇治疗后，MMP-14和MMP-2明显降低（p<0.01）。tgf - β1增加食管上皮HET1A细胞MMP-2的表达和分泌。MMP-2和-14在儿童EoE患者中升高，在局部皮质类固醇治疗后显著降低。tgf - β1增加食管上皮细胞的MMP-2。这暗示了先前未被认识到的MMPs在EoE相关的食管重构中的作用，以及通过tgf - β1的潜在正反馈循环。
Eosinophilic esophagitis (EoE) is a chronic antigen mediated disease in children and adults associated with substantial esophageal remodeling and fibrosis. The expression of the remodeling-associated matrix metalloproteinases (MMPs) has not been previously detailed in EoE. MMP-2 and -14 expression and cellular localization was assessed using qPCR and immunohistochemistry/immunofluorescence in EoE fibroblasts, active and inactive pediatric EoE biopsies, and non-diseased control biopsies. The effect of TGFβ1 treatment on MMP-2 expression in cultured esophageal epithelial (HET1A) cells was analyzed. MMP-2 and -14 mRNA were expressed in EoE fibroblasts and biopsies. Proliferating epithelial cells produced MMP-14 more abundantly in EoE than in controls (p<0.001) and the degree of epithelial MMP-14 expression correlated positively with basal zone hyperplasia (r=0.65, p=0.002). EoE lamina propria had higher numbers of MMP-2 and -14 positive cells (906 ± 167 and 701 ± 93 cells/mm2) as compared with controls (258 ± 93 p<0.01 and 232 ± 54 cells/mm2 p<0.01) and MMP-14 expression correlated with the severity of fibrosis. Following therapy with topical corticosteroids, MMP-14 and MMP-2 were significantly diminished (p<0.01). TGFβ1 increased the expression and secretion of MMP-2 from esophageal epithelial HET1A cells. MMP-2 and -14 are elevated in pediatric EoE subjects and significantly decrease following topical corticosteroid therapy. TGFβ1 increases MMP-2 in esophageal epithelial cells. This alludes to previously unappreciated role for MMPs in EoE associated esophageal remodeling and a potential positive feedback loop via TGFβ1.