| Autor: |
Qianhua Zheng, Zhi-Wei Li, Xinye Luo, Wenchuan Qi, Yilu Jiang, Fanrong Liang, Bai-Tong Liu, Ding-jun Cai |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.21203/rs.3.rs-929701/v1 |
| Popis: |
Selecting routine points on related meridians is widely accepted as the foundational principle of acupuncture. When the body is suffering disease or injury, corresponding acupoints are thought to be activated and manifest in several sensitized forms. Sensitized acupoints hold high clinical value as a reflection of disease activity on the body surface. Mast cells have been implicated in the process of acupoint sensitization but the underlying regulatory mechanisms remain unclear. In the present study, we evaluated ST36 as a sensitized acupoint in the monosodium iodoacetate-induced knee osteoarthritis rat model. We first confirmed sensitization at the ST36 acupoint through decreases in the acupoint mechanical pain threshold and instructively found an accompanying increase in skin mast cell degranulation. Thereafter, we used highthroughput RNA sequencing to reveal potential molecular mechanisms of acupoint sensitization. We showed that rno-miR-199a-3p was highly expressed in the sensitized ST36 acupoint and its expression was associated with mast cells. Functional experiments revealed that overexpression of rno-miR-199a-3p increased mast cell histamine release whereas inhibition of rno-miR-199a-3p decreased histamine release. Mechanistically, we established rno-miR-199a-3p acted to inhibit neural precursor cell expressed developmentally down-regulated 4 (Nedd4) protein expression through miRNA-mediated targeting of the 3’-UTR of Nedd4 mRNA. Moreover, we found ectopic expression of Nedd4 antagonized histamine release in mast cells and blocked the actions of rno-miR-199a-3p overexpression. Thus, our study establishes that mast cells participate in the process of acupoint sensitization, and further reveals a novel miRNA-based mechanism which is crucial for further understanding of acupoint sensitization and acupuncture applications. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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