小肠 TGFβ1 和 TGFβ3 的差异表达是纤维性克罗恩病患者肠道狭窄的特征。

IF 2.1 4区 生物学 Q4 CELL BIOLOGY
Histochemistry and Cell Biology Pub Date : 2024-09-01 Epub Date: 2024-05-05 DOI:10.1007/s00418-024-02290-0
Steven Levitte, Ibaad Khan, Violet Iyahen, James Ziai, John Gubatan, Rebecca Sheng, Sara B Glickstein, Tianhe Sun, K T Park, Jacqueline McBride, Mary Keir
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引用次数: 0

摘要

小肠狭窄仍然是克罗恩病的一个令人衰弱的后果,并导致患者预后不佳。最近,TGFβ被认为是肠纤维化的重要驱动因素。我们利用原位杂交技术研究了克罗恩病患者回肠狭窄处 TGFβ 同工酶的定位,以了解 TGFβ 在狭窄形成中的作用。与无克罗恩病患者的正常回肠相比,狭窄处粘膜的TGFβ1更高,而狭窄处粘膜下层的TGFβ3更高(分别为p = 0.02和p = 0.044)。我们将这些发现与单细胞转录组学相关联,结果表明 TGFβ3 转录物总体上非常罕见,这可能部分解释了为什么迄今为止 TGFβ3 在肠纤维化中的作用仍不明确。在发炎与未发炎的回肠中,成纤维细胞或 B 细胞的 TGFβ1 和/或 TGFβ3 表达没有明显差异。我们讨论了这些发现对治疗纤维狭窄性克罗恩病患者的治疗开发策略的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Differential expression of small bowel TGFβ1 and TGFβ3 characterizes intestinal strictures in patients with fibrostenotic Crohn's disease.

Differential expression of small bowel TGFβ1 and TGFβ3 characterizes intestinal strictures in patients with fibrostenotic Crohn's disease.

Small bowel strictures remain a debilitating consequence of Crohn's disease and contribute to poor outcomes for patients. Recently, TGFβ has been identified as an important driver of intestinal fibrosis. We studied the localization of TGFβ isoforms in ileal strictures of patients with Crohn's disease using in situ hybridization to understand TGFβ's role in stricture formation. The mucosa of strictures was characterized by higher TGFβ1 while the stricture submucosa showed higher TGFβ3 compared to normal ileum from patients without Crohn's disease (p = 0.02 and p = 0.044, respectively). We correlated these findings with single-cell transcriptomics which demonstrated that TGFβ3 transcripts overall are very rare, which may partially explain why its role in intestinal fibrosis has remained unclear to date. There were no significant differences in fibroblast or B cell TGFβ1 and/or TGFβ3 expression in inflamed vs. noninflamed ileum. We discuss the implications of these findings for therapeutic development strategies to treat patients with fibrostenotic Crohn's disease.

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来源期刊
Histochemistry and Cell Biology
Histochemistry and Cell Biology 生物-细胞生物学
CiteScore
4.90
自引率
8.70%
发文量
112
审稿时长
1 months
期刊介绍: Histochemistry and Cell Biology is devoted to the field of molecular histology and cell biology, publishing original articles dealing with the localization and identification of molecular components, metabolic activities and cell biological aspects of cells and tissues. Coverage extends to the development, application, and/or evaluation of methods and probes that can be used in the entire area of histochemistry and cell biology.
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