Nrf2-induced miR-23a-27a-24-2 cluster modulates damage repair of intestinal mucosa by targeting the Bach1/HO-1 axis in inflammatory bowel diseases
Dun Su, Xingwen Wang, Yan Ma, Jinghua Hao, Jinshen Wang, Yongqu Lu, Yulin Liu, Xingfang Wang, Li Zhang
Abstract
IBD is an idiopathic, chronic autoimmune disease associated with intense oxidative stress. As a master modulator of oxidative stress, Nrf2 has an important anti-inflammatory role in colitis by activating HO-1 transcription. Meanwhile, HO-1 expression is transcriptionally suppressed by Bach1. The Nrf2-activated HO-1 transcription depends on the inactivation of Bach1. However, how Bach1 is inactivated and how Nrf2, Bach1 and HO-1 participate in IBD remains elusive. We found that in response to inflammatory stimuli, Nrf2-induced transcription of miR-23a-27a-24-2 cluster directly inhibits Bach1 expression by binding to the 3'UTR and thereby relieved the Bach1-mediated suppression of HO-1. Besides, elevated miR-23a, miR-27a and miR-24-2 promotes the proliferation and wound healing through regulating Bach1/HO-1 expression in SW480 cell. Additionally, miR-23a, miR-27a and miR-24-2 exert a protective effect on the intestinal mucosa in DSS-induced colitis mouse model. In conclusion, our study revealed that the Nrf2/miR-23a-27a-24-2/Bach1/HO-1 regulatory axis promotes the damage repair of intestinal mucosa during the development of inflammatory bowel diseases.