期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 24, 期 1, 页码 405-417出版社
WILEY
DOI: 10.1111/jcmm.14744
关键词
endometritis; inflammation; miR-148a; NF-kappa B; TLR4
资金
- National Natural Science Foundation of China [31772816, 31972744]
- Fujian Provincial Key Laboratory for the Prevention and Control of Animal Infectious Diseases and Biotechnology [2018KF05]
Endometritis is a postnatal reproductive disorder disease, which leads to great economic losses for the modern dairy industry. Emerging evidence indicates that microRNAs (miRNAs) play a pivotal role in a variety of diseases and have been identified as critical regulators of the innate immune response. Recent miRNome profile analysis revealed an altered expression level of miR-148a in cows with endometritis. Therefore, the present study aims to investigate the regulatory role of miR-148a in the innate immune response involved in endometritis and estimate its potential therapeutic value. Here, we found that miR-148a expression in lipopolysaccharide (LPS)-stimulated endometrial epithelial cells was significantly decreased. Our results also showed that overexpression of miR-148a using agomiR markedly reduced the production of pro-inflammatory cytokines, such as IL-1 beta and TNF-alpha. Moreover, overexpression of miR-148a also suppressed NF-kappa B p65 activation by targeting the TLR4-mediated pathway. Subsequently, we further verified that miR-148a repressed TLR4 expression by binding to the 3 '-UTR of TLR4 mRNA. Additionally, an experimental mouse endometritis model was employed to evaluate the therapeutic value of miR-148a. In vivo studies suggested that up-regulation of miR-148a alleviated the inflammatory conditions in the uterus as evidenced by H&E staining, qPCR and Western blot assays, while inhibition of miR-148a had inverse effects. Collectively, pharmacologic stabilization of miR-148a represents a novel therapy for endometritis and other inflammation-related diseases.
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