A role for age-associated alterations in esophageal epithelium in eosinophilic esophagitis-associated fibrosis.
A role for age-associated alterations in esophageal epithelium in eosinophilic esophagitis-associated fibrosis.
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DOI：
10.3389/falgy.2022.983412
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发表时间：
2022
影响因子：
--
通讯作者：
Whelan, Kelly A.
中科院分区：
文献类型：
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作者：
Klochkova, Alena;Fuller, Annie D.;Miller, Riley;Karami, Adam L.;Panchani, Surali R.;Natarajan, Shruthi;Mu, Anbin;Jackson, Jazmyne L.;Klein-Szanto, Andres J.;Muir, Amanda B.;Whelan, Kelly A.
上皮下纤维化发生在嗜酸性食管炎(EoE)患者的一部分，并与食道狭窄相关。虽然推动EoE纤维化的机制仍不完全清楚，但来自实验系统的发现支持上皮-成纤维细胞串扰在这种类型的组织重塑中的作用。目前的研究范式认为EOE是一种进行性的纤维狭窄疾病，老年患者的纤维化程度与疾病的慢性化程度有关。在目前的研究中，我们提供的证据表明，老化的食道上皮生物学改变也可能导致EoE相关的纤维化。我们发现，在相同的时间段内，使用MC903/卵清蛋白方案在青年和老年小鼠中诱导EoE炎症会导致老年动物固有层厚度的增加。此外，与年轻小鼠相比，老年小鼠的上皮细胞在胶原盒收缩试验中限制成纤维细胞收缩的效率较低。最后，为了确定衰老的食道上皮细胞可能刺激纤维化重塑的潜在机制，我们在年轻和老年小鼠身上进行了细胞因子阵列实验。这些研究具有重要意义，因为识别导致纤维重塑的年龄相关因素可能有助于制定早期发现、预防和治疗纤维狭窄EoE的策略。
Subepithelial fibrosis occurs in a subset of eosinophilic esophagitis (EoE) patients and is associated with esophageal stricture. While mechanisms driving EoE fibrosis remain incompletely understood, findings from experimental systems support roles for epithelial-fibroblast crosstalk in this type of tissue remodeling. The current paradigm presents EoE as a progressive fibrostenotic disease in which aged patients develop fibrosis as a function of disease chronicity. In the current study we provide evidence that altered epithelial biology in the aging esophagus may also contribute to EoE-associated fibrosis. We find that induction of EoE inflammation in young and aged mice using the MC903/Ovalbumin protocol for the same time period results in increased lamina propria thickness uniquely in aged animals. Additionally, epithelial cells from aged mice less efficiently limit fibroblast contractility in collagen plug contraction assays compared to those from their young counterparts. Finally, to identify potential mechanisms through which aged esophageal epithelial cells may stimulate fibrotic remodeling, we perform cytokine array experiments in young and aged mice. These studies are significant as identification of age-associated factors that contribute to fibrotic remodeling may aid in the design of strategies toward early detection, prevention, and therapy of fibrostenotic EoE.
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DOI：
10.1186/s12979-020-00205-w
发表时间：
2020-11-14
期刊：
Immunity & ageing : I & A
影响因子：
--
作者：
Chen M;Yang N;Lechner J;Toth L;Hogg R;Silvestri G;Chakravarthy U;Xu H
通讯作者：
Xu H
DOI：
10.1126/science.aau3879
发表时间：
2018-11-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Martincorena I;Fowler JC;Wabik A;Lawson ARJ;Abascal F;Hall MWJ;Cagan A;Murai K;Mahbubani K;Stratton MR;Fitzgerald RC;Handford PA;Campbell PJ;Saeb-Parsy K;Jones PH
通讯作者：
Jones PH
影响因子：
7.7
作者：
Dellon ES;Kim HP;Sperry SL;Rybnicek DA;Woosley JT;Shaheen NJ
通讯作者：
Shaheen NJ
影响因子：
7.7
作者：
Eluri, Swathi;Runge, Thomas M.;Dellon, Evan S.
通讯作者：
Dellon, Evan S.
单细胞转录组分析揭示了鼠食管上皮的细胞多样性。
影响因子：
16.6
作者：
通讯作者：
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