RGMa regulates CCL5 expression via the BMP receptor in experimental autoimmune encephalomyelitis mice and endothelial cells

Tang,Shi; Su,Bao; Tao,Tao; Yan,Weiping; Zhang,Rongrong; Qin,Xinyue; Feng,Jinzhou

doi:10.3892/mmr.2022.12601

RGMa regulates CCL5 expression via the BMP receptor in experimental autoimmune encephalomyelitis mice and endothelial cells

Authors:
- Shi Tang
- Bao Su
- Tao Tao
- Weiping Yan
- Rongrong Zhang
- Xinyue Qin
- Jinzhou Feng
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Affiliations: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Neurology, Guangrao District People's Hospital, Dongying, Shandong 257300, P.R. China
Published online on: January 13, 2022 https://doi.org/10.3892/mmr.2022.12601
Article Number: 85
Copyright: © Tang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). Repulsive guidance molecule a (RGMa) has been indicated to act as a bone morphogenetic protein (BMP) co‑receptor, enhancing BMP signalling activity. However, the role and downstream pathways of the BMP signalling pathway mediated by RGMa have yet to be fully elucidated. A recent study revealed that C‑C motif chemokine ligand 5 (CCL5) has a major role in the pathogenesis of MS via the recruitment of macrophages and T‑lymphocytes into the CNS. The present study aimed to evaluate whether RGMa regulates CCL5 via the BMP pathway in MS. The results demonstrated that RGMa regulated CCL5 expression in a BMP ligand‑dependent manner in experimental autoimmune encephalomyelitis (EAE) mice in vivo and in endothelial cells in vitro. First, specific inhibition of the expression of RGMa via RNA interference led to a significant reduction of the expression of RGMa and this was associated with a significant delay of EAE, an alleviated disease course and downregulation of CCL5 expression at both the protein and mRNA levels. Furthermore, exogenous noggin, an extracellular antagonist of BMP ligand, abolished the induction effect of RGMa on CCL5 in endothelial cells. Taken together, these results suggested that RGMa is an important regulator of MS and inflammatory mediators such as CCL5, and the present results should prove to be useful in terms of further elucidating the RGMa‑BMP receptor signalling pathway and the pathogenesis of RGMa on MS as far as the involvement of blood‑brain barrier permeability is concerned.

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