Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Surgery, VA North Texas Health Care System, University of Texas Southwestern Medical Center, Dallas, Texas.
Cell Mol Gastroenterol Hepatol. 2018 Jun 27;6(4):389-404. doi: 10.1016/j.jcmgh.2018.06.007. eCollection 2018.
BACKGROUND & AIMS: After esophagojejunostomy, rodents develop reflux esophagitis and a columnar-lined esophagus with features of Barrett's metaplasia. This rodent columnar-lined esophagus has been proposed to develop from cellular reprogramming of progenitor cells, but studies on early columnar-lined esophagus development are lacking. We performed a systematic, histologic, and immunophenotypic analysis of columnar-lined esophagus development in rats after esophagojejunostomy.
At various times after esophagojejunostomy in 52 rats, the esophagus was removed and tissue sections were evaluated for type, location, and length of columnar lining. Molecular characteristics were evaluated by immunohistochemistry and immunofluorescence.
At week 2, ulceration was seen in esophageal squamous epithelium, starting distally at the esophagojejunostomy anastomosis. Re-epithelialization of the distal ulcer segment occurred via proliferation and expansion of immature-appearing glands budding directly off jejunal crypts, characteristic of wound healing. The columnar-lined esophagus's immunoprofile was similar to jejunal crypt epithelium, and columnar-lined esophagus length increased significantly from 0.15 mm (±0.1 SEM) at 2 weeks to 5.22 mm (±0.37) at 32 weeks. Neoglands were found within esophageal ulcer beds, and spindle-shaped cells expressing epithelial-mesenchymal transition markers were found at the columnar-lined esophagus's leading edge. Only proliferative squamous epithelium was found at the proximal ulcer border.
After esophagojejunostomy in rats, metaplastic columnar-lined esophagus develops via a wound healing process that does not appear to involve cellular reprogramming of progenitor cells. This process involves EMT-associated migration of jejunal cells into the esophagus, where they likely have a competitive advantage over squamous cells in the setting of ongoing gastroesophageal reflux disease.
在进行食管空肠吻合术后，啮齿动物会发展为反流性食管炎和具有 Barrett 化生特征的柱状上皮食管。这种啮齿动物的柱状上皮食管被认为是由祖细胞的细胞重编程发展而来，但早期柱状上皮食管发育的研究尚缺乏。我们对食管空肠吻合术后大鼠的柱状上皮食管发育进行了系统的组织学和免疫表型分析。
在 52 只大鼠进行食管空肠吻合术后的不同时间，切除食管并评估组织切片的柱状上皮衬里的类型、位置和长度。通过免疫组织化学和免疫荧光评估分子特征。
在第 2 周，食管鳞状上皮出现溃疡，从食管空肠吻合口的远端开始。远端溃疡段的再上皮化通过增殖和扩展直接来自空肠隐窝的不成熟腺体来实现，这是愈合的特征。柱状上皮食管的免疫表型与空肠隐窝上皮相似，柱状上皮食管的长度从第 2 周的 0.15 毫米（±0.1 SEM）显著增加到第 32 周的 5.22 毫米（±0.37）。在食管溃疡床中发现了新的腺体，在柱状上皮食管的前缘发现了表达上皮-间充质转化标志物的梭形细胞。仅在近端溃疡边界处发现有增殖性鳞状上皮。
在大鼠进行食管空肠吻合术后，化生的柱状上皮食管通过愈合过程发展，该过程似乎不涉及祖细胞的细胞重编程。这个过程涉及到与 EMT 相关的空肠细胞向食管的迁移，在持续的胃食管反流病中，这些细胞在与鳞状细胞竞争中可能具有优势。
