1. Academic Validation
  2. TNF-α up-regulates Nanog by activating NF-κB pathway to induce primary rat spinal cord astrocytes dedifferentiation

TNF-α up-regulates Nanog by activating NF-κB pathway to induce primary rat spinal cord astrocytes dedifferentiation

  • Life Sci. 2021 Dec 15;287:120126. doi: 10.1016/j.lfs.2021.120126.
Zhenfei Ding 1 Ce Dai 2 Wenshan Shan 3 Rui Liu 3 Wei Lu 3 Weilu Gao 3 Hui Zhang 3 Wei Huang 4 Jianzhong Guan 5 Zongsheng Yin 6
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical College, 287#Chang Huai Road, Bengbu 230071, Anhui, China; Department of Orthopaedics, The Second People's Hospital of Hefei, Intersection of Guangde Road and Leshui Road, Hefei 230011, Anhui, China.
  • 2 Department of Orthopaedics, The Second People's Hospital of Hefei, Intersection of Guangde Road and Leshui Road, Hefei 230011, Anhui, China.
  • 3 Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, 218#Ji Xi Road, Hefei 230032, Anhui, China.
  • 4 Department of Orthopaedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China. Electronic address: zgkdhwei@ustc.edu.cn.
  • 5 Department of Orthopaedics, The First Affiliated Hospital of Bengbu Medical College, 287#Chang Huai Road, Bengbu 230071, Anhui, China; Anhui Key Laboratory of Tissue Transplantation, 2600#Dong Hai Avenue, Bengbu 233030, Anhui, China. Electronic address: jzguan2002@163.com.
  • 6 Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, 218#Ji Xi Road, Hefei 230032, Anhui, China. Electronic address: anhyzs@126.com.
Abstract

Aims: Astrocytes re-acquire stem cell potential upon inflammation, thereby becoming a promising source of cells for regenerative medicine. Nanog is an essential transcription factor to maintain the characteristics of stem cells. We aimed to investigate the role of Nanog in astrocyte dedifferentiation.

Main methods: TNF-α was used to induce the dedifferentiation of primary rat spinal cord astrocytes. The expression of immature markers CD44 and Musashi-1 was detected by qRT-PCR and immunofluorescence. The Nanog gene is knocked down by small interference RNA. Nanog expression was measured by qRT-PCR and western blotting. BAY 11-7082 was used to suppress NF-κB signals in astrocytes. NF-κB signaling was evaluated by Western blotting.

Key findings: Our results showed that TNF-α promoted the re-expression of CD44 and Musashi-1 in astrocytes. Dedifferentiated astrocytes could be induced to differentiate into oligodendrocyte lineage cells indicating that the astrocytes had pluripotency. In addition, TNF-α treatment activated NF-κB signaling pathway and up-regulated Nanog. Knockdown of Nanog reversed the increase of CD44 and Musashi-1 induced by TNF-α without affecting the activation of NF-κB signaling. Importantly, blocking NF-κB signaling by BAY 11-7082 inhibited the expression of immature markers suggesting that TNF-α induces dedifferentiation of astrocytes through the NF-κB signaling pathway. BAY 11-7082 could also inhibit the expression of Nanog, which indicated that Nanog was regulated by NF-κB signaling pathway.

Significance: These findings indicate that activation of the NF-κB signaling pathway through TNF-α leads to astrocytes dedifferentiation via Nanog. These results expand our understanding of the mechanism of astrocytes dedifferentiation.

Keywords

Astrocyte; Dedifferentiation; Inflammation; NF-κB; Nanog.

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