Differential upregulation of the hypothetical transmembrane protein 66 (TMEM66) in multiple sclerosis patients with potential inflammatory response

Abstract

Abstract. The prevalence of multiple sclerosis (MS) in the Gulf region has markedly increased during the last decade, but the mechanisms of the disease have not been investigated. The present study aimed to understand the molecular processes involved in the disease development of the recently emerged MS in this population using microarray technology to investigate differentially-expressed novel genes in MS patients compared to healthy-matched subjects. The expression of the upregulated genes was confirmed by quantitative polymerase chain reaction (qPCR). Furthermore, gene cloning, protein expression and purification were performed followed by testing of the obtained recombinant protein on biological assays, including cell proliferation and cytokine mRNA detection by reverse transcriptase-qPCR. The results showed that out of ~50,000 genes, the hypothetical transmembrane protein-66 gene (TMEM66) exhibited a 3 times higher expression in MS patients compared to healthy subjects. The TMEM66 gene was cloned and its protein showed marked immunological activity relevant to MS since significant proliferation (P<0.05) and augmented induction of the proinflammatory cytokines, interleukin (IL)-6, interferon-γ, tumor necrosis factor-α, and the chemokines, chemokine ligand 5/chemokine receptor 5, macrophage inflammatory protein 1α (MIP-1α) and MIP-1β were recorded, but not the anti-inflammatory cytokines, IL-4 or IL-2. In conclusion, TMEM66 may be associated with the molecular events of MS and may be considered as an MS biomarker for future personalized medicine management approaches.

Retracted: MicroRNA‐339‐3p alleviates inflammation and edema and suppresses pulmonary microvascular endothelial cell apoptosis in mice with severe acute pancreatitis‐associated acute lung injury by regulating Anxa3 via the Akt/mTOR signaling pathway

“…IL‐6 acts as an important mediator for inflammation, and overexpressed IL‐6 has a potential risk which may cause additional cell death, and neurological dysfunction . Upregulated Anxa3 and induced proinflammatory cytokines TNF‐α and IL‐6 were both shown in patients with multiple sclerosis, which indicated that Anxa3 may induce TNF‐α, and IL‐6 . There was a study also found that SAP mice had higher AMS levels, MPO activity in the lung tissues, and value of W/D .…”

Cholecalciferol Supplementation Induced Up-Regulation of SARAF Gene and Down-Regulated miR-155-5p Expression in Slovenian Patients with Multiple Sclerosis

“…However, our results are in discrepancy with a previous study that found that SARAF may be preferentially expressed in patients with multiple sclerosis [ 43 ]. The study showed that SARAF induced the expression of pro-inflammatory cytokines, but not anti-inflammatory cytokines [ 43 ].…”

“…However, our results are in discrepancy with a previous study that found that SARAF may be preferentially expressed in patients with multiple sclerosis [ 43 ]. The study showed that SARAF induced the expression of pro-inflammatory cytokines, but not anti-inflammatory cytokines [ 43 ]. These findings are partially supported with findings that indicate that SARAF contributes to T-cell activation through the promotion of TCR-mediated signaling via Ca 2+ –calcineurin–nuclear factor of the activated T-cells (NFAT) pathway [ 42 ].…”

Bidirectional regulation of calcium release–activated calcium (CRAC) channel by SARAF

“…In summary, the dual regulatory effect of SARAF on CRAC channel activity presented in this work sheds light on a poorly characterized step during CRAC channel activation and provides an important framework for understanding the physiological role of SARAF in different cell types and its potential involvement in different pathophysiological conditions, including pancreatitis ( Son et al, 2019 ), cancer ( Romanuik et al, 2009 ; Iżykowska et al, 2017 ), neurodegenerative diseases ( Iżykowska et al, 2017 ; Taha et al, 2015 ; Twine et al, 2011 ), and cardiovascular diseases ( Yang et al, 2019 ; Dai et al, 2018 ; Camargo and Azuaje, 2008 ; Sanlialp et al, 2020 ; La Russa et al, 2020 ).…”