Electroacupuncture Alleviates Functional Dyspepsia by Targeting miR-221-3p to Regulate c-kit/SCF and Raf/Erk Signaling

Background: Functional dyspepsia (FD) is a gastrointestinal disorder associated with epigastric pain and fullness, with symptoms such as anxiety and depression. Electroacupuncture (EA) has emerged as a potential therapeutic strategy to treat FD via electrical stimulation at specific acupoints of the body and has previously been demonstrated to be effective in promoting gastric motility and attenuating the symptoms of FD. However, the mechanisms underlying the effect of EA remain elusive. Results: : Herein, we constructed an in vivo model of FD in rats and performed EA on FD-induced rats. Preliminary bioinformatic analysis through RNA sequencing revealed that differentially expressed microRNAs exist between non-treated and EA-treated rats subjected to EA. Among them, miR-221-3p was associated with the target gene c-kit, the expression of which is closely linked to interstitial cells of Cajal (ICCs) and gap junction intercellular communication, factors critically implicated in gastrointestinal motility. We further proved that miR-221-3p overexpression aggravated FD, but EA downregulated miR-221-3p to alleviate the symptoms of FD. The mechanisms of action underlying the effect of EA involve an increase in c-kit + ICCs, upregulation of stem cell factor and connexin 43, and enhanced Raf/Erk signaling. Conclusions: : Our findings suggest that EA is an effective method of managing FD by regulating miR-221-3p, the c-kit/stem cell factor axis, and Raf/Erk signaling, reinforcing the strong role of gap junction intercellular communication in gastrointestinal motility.