The crosstalk between IGF-1R and ER-α in the proliferation and anti-inflammation of nucleus pulposus cells.

R-S Chen, X-B Zhang, X-T Zhu, C-S Wang

European review for medical and pharmacological sciences 2020 Jun

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Insulin-like growth factors-1 receptor (IGF-1R) and estrogen receptor (ER) are reported to co-express and engage in crosstalk involving in the synergistic effect of various aspects. It is unknown whether this crosstalk exists in the nucleus pulposus (NP) cells. We aimed to investigate the interaction between IGF-1R and ER-α in regulating NP cell proliferation and inflammation response under IGF-1 stimulation. We analyzed the IGF-1, IGF-1R, and ER-α in different degenerated degree human NP tissues. NP cells were cultured with IGF-1 protein with or without the inhibitor of IGF-1R or ER-α to investigate their effects on the proliferation and inflammation response. In addition, we also upregulated the IFG-1R and ER-α expression by plasmid transfection to investigate the impact on each other. The content of IGF-1, IFG-1R, and ER-α was analyzed by enzyme-linked immunosorbent assay (ELISA). The proliferative cell rate was determined by flow cytometry. Additionally, intracellular collagen-II, p16, PCNA, IL-1β, IL-6, TNF-α, and MMP-13 expression were also detected. We found IGF-1, IFG-1R, and ER-α content were decreased in higher degenerated NP tissues. IGF-1 protein treatment upregulated the IFG-1R and ER-α expression and promoted NP cell proliferation, collagen-II, and PCNA expression. However, the suppression of IGF-1R (or ER-α) weakened the IGF-1 induced collagen-II expression, proliferation, and anti-inflammation effects on NP cells, decreased ER-α (or IGF-1R) expression, and partly reversed the protective effect of NP cells caused by IGF-1 Similarly, the upregulation of one of IGF-1R and ER-α may increase the other as well. There is an interaction between IGF-1R and ER-α acts synergistically to promote the proliferation and suppress inflammation in NP cells.

Citation

R-S Chen, X-B Zhang, X-T Zhu, C-S Wang. The crosstalk between IGF-1R and ER-α in the proliferation and anti-inflammation of nucleus pulposus cells. European review for medical and pharmacological sciences. 2020 Jun;24(11):5886-5894