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首页> 外文期刊>American Journal of Physiology >Roles of epidermal growth factor and Na+/H+ exchanger-1 in esophageal epithelial defense against acid-induced injury.
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Roles of epidermal growth factor and Na+/H+ exchanger-1 in esophageal epithelial defense against acid-induced injury.

机译：表皮生长因子和Na + / H +交换子1在食管上皮防御酸诱导的损伤中的作用。

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摘要

Epidermal growth factor (EGF) is predominantly secreted by salivary glands and activates Na(+)/H(+) exchanger-1 (NHE-1), which regulates intracellular pH (pH(i)). We investigated the roles of EGF and NHE-1 in esophageal epithelial defense against acid using human esophageal epithelial cell lines and a rat chronic esophagitis model. Esophageal epithelial cells were incubated with acidified medium in the absence or presence of EGF. Cell viability and changes in pH(i) were measured. Chronic acid reflux esophagitis was induced in rats with and without sialoadenectomy. Esophageal lesion index, epithelial proliferation, and expression of EGF receptors and NHE-1 were examined. EGF protected esophageal epithelial cells against acid in a dose-dependent manner, and the cytoprotective effect of EGF was completely blocked by treatment with NHE-1 inhibitors. Tyrosine kinase, calmodulin, and PKC inhibitors significantly inhibited cytoprotection by EGF, whereas MEK, phosphatidylinositol 3-kinase, and PKA inhibitors had no effect. EGF significantly increased pH(i) recovery after NH(4)Cl pulse acidification, and this increase in pH(i) recovery was significantly blocked by inhibitors of calmodulin and PKC. Sialoadenectomy led to an increase in the severity of chronic esophagitis but affected neither epithelial proliferation nor expression of EGF receptors. Expression of NHE-1 mRNA was increased in esophagitis and upregulated in rats with sialoadenectomy. The increasing severity of esophagitis in rats with sialoadenectomy was prevented by exogenous administration of EGF. In conclusion, EGF protects esophageal epithelial cells against acid through NHE activation via Ca(2+)/calmodulin and the PKC pathway. Deficiency in endogenous EGF is associated with increased severity of esophagitis. EGF and NHE-1 play crucial roles in esophageal epithelial defense against acid.
机译：表皮生长因子（EGF）主要由唾液腺分泌，并激活Na（+）/ H（+）交换子1（NHE-1），后者调节细胞内pH（pH（i））。我们使用人食管上皮细胞系和大鼠慢性食管炎模型研究了EGF和NHE-1在食管上皮对酸的防御中的作用。在不存在或存在EGF的情况下，将食管上皮细胞与酸化培养基孵育。测量细胞活力和pH（i）的变化。在进行和未进行涎腺切除术的大鼠中诱发了慢性胃酸反流性食管炎。检查食管病变指数，上皮增殖，EGF受体和NHE-1的表达。 EGF以剂量依赖的方式保护食管上皮细胞免受酸侵害，并且用NHE-1抑制剂治疗可完全阻断EGF的细胞保护作用。酪氨酸激酶，钙调蛋白和PKC抑制剂可显着抑制EGF对细胞的保护，而MEK，磷脂酰肌醇3-激酶和PKA抑制剂则无作用。 EGF在NH（4）Cl脉冲酸化后显着提高了pH（i）的回收率，而钙调蛋白和PKC抑制剂则明显阻止了pH（i）回收率的提高。 Sialoadenectomy导致慢性食管炎的严重程度增加，但既不影响上皮的增殖，也不影响EGF受体的表达。在唾液腺切除术大鼠中，NHE-1 mRNA的表达在食管炎中升高，并上调。通过外用EGF可以防止唾液腺切除术大鼠食管炎的严重程度增加。总之，EGF通过经由Ca（2 +）/钙调蛋白和PKC途径的NHE活化来保护食道上皮细胞免受酸侵害。内源性EGF缺乏与食管炎的严重程度增加有关。 EGF和NHE-1在食管上皮对酸的防御中起关键作用。

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