Increased expression of endothelin‐1 and endothelin receptor A in reflux esophagitis and Barrett's esophagus

Barrett's esophagus (BE) is considered a complication of the inflammation provoked by acid and bile reflux. Endothelin‐1 (ET‐1) expresses in various cells during inflammatory process. However, the role of ET‐1 in human inflamed and uninflamed esophageal tissue is unknown. The present study aimed to examine the expression of ET‐1 and its receptors in human reflux esophagitis (RE) and BE. Endoscopic biopsies of normal squamous epithelium (NSE) (n = 20), RE (n = 22), and long segment BE (n = 14) were obtained. The segmental degree of endoscopic and histopathological inflammation was graded, and immunohistochemistry and real‐time quantitative polymerase chain reaction were used to determine the expression of ET‐1 and endothelin receptor A (ET(A)R) and endothelin receptor B (ET(B)R). ET‐1 and ET(A)R messenger RNA (mRNA) levels were higher in RE than in NSE (3.25 ± 1.78 vs. 1.10 ± 0.71, P = 0.000; 2.13 ± 1.06 vs. 1.12 ± 0.64, P = 0.001, respectively). In BE, relative ET‐1 mRNA levels in the proximal segment were higher than in the distal segment (3.03 ± 1.83 vs. 1.16 ± 0.70, P = 0.004) and in normal esophageal epithelium (P = 0.002). There was no significantly difference of ET(A)R mRNA levels between the proximal segment and the distal segment (1.99 ± 1.28 vs. 1.14 ± 0.67, P = 0.072). ET(B)R mRNA expression was unaltered between the groups. Furthermore, immunohistochemistry demonstrated that ET‐1 expression increased significantly in RE (51.18 ± 30.14) compared with those in NSE (21.10 ± 18.17, P = 0.000) and in distal BE segment (28.02 ± 24.92, P = 0.022). There were more ET‐1 positive cells in proximal BE segment (50.07 ± 25.88) than in distal BE segment (P = 0.030) and in NSE (P = 0.001). ET‐1 expression increased in a stepwise manner with the growing degree of inflammation, and there were significant differences between mild, moderate, and marked degree esophagitis (36.08 ± 27.84, 65.86 ± 11.82, 98.00 ± 8.49, P = 0.003, respectively). However, expression of receptors remained unchanged. This study demonstrates that over‐expression of ET‐1 and ET(A)R in esophagitis may be related to the inflammatory process. ET‐1 may play a significant role in the progression of Barrett's metaplasia.