High-dose TGF-β1 degrades human nucleus pulposus cells via ALK1-Smad1/5/8 activation
Autor: | Yongming Sun, Weiwei Chen, Fengxiang Zhang, Tao Lin, Zhiqiang Qu |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cancer Research Cell SMAD Matrix metalloproteinase 03 medical and health sciences nucleus pulposus cells 0302 clinical medicine Immunology and Microbiology (miscellaneous) Downregulation and upregulation medicine Receptor transforming growth factor-β1 Smad Oncogene intervertebral disc degeneration Chemistry General Medicine Articles Cell biology 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Tumor necrosis factor alpha ALK tyrosine kinase receptor 1/5 Transforming growth factor |
Zdroj: | Experimental and Therapeutic Medicine |
ISSN: | 1792-1015 1792-0981 |
Popis: | Transforming growth factor β1 (TGF-β1) can promote the proliferation and differentiation of intervertebral disc cells and participates in its repair process. However, whether TGF-β1 engages in the process of disc degeneration has not yet been fully elucidated. The present study aimed to investigate the function of high-dose TGF-β1 on the metabolism of nucleus pulposus cells (NPCs). TGF-β1 levels in human degenerative intervertebral disc tissues and tumor necrosis factor (TNF)-α-induced degenerative NPCs were analyzed. Furthermore, NPCs were treated with TGF-β1 and inhibitors of TGF-β1 receptors [ALK tyrosine kinase receptor (ALK) 1 and ALK5] to determine the effect of the receptors in the mediation of NPC degeneration. The NPC state was determined by the components of secretory collagen I/II, tissue inhibitor of metalloproteinase-3 (TIMP-3) and matrix metalloproteinase (MMP)-13. The mRNA expression of Smad1/2/3/5/8, the downstream gene of TGF-β1 mediated by ALK, was also measured. Results showed that TGF-β1 and ALK1 were positively associated with the degree of degeneration of NP or NPCs in vitro, but negatively associated with ALK5. Furthermore, high-doses of TGF-β1 suppressed collagen II, but enhanced collagen I, TIMP-3, MMP-13, ALK1/5 and Smad1/2/3/5/8 expression. ALK5 inhibition induced the suppression of Smad2/3 and aggravated high-dose TGF-β1-induced NPC degeneration, as shown by the reduction in collagen II and increase in collagen I, TIMP-3 and MMP-13. By contrast, ALK1 inhibition resulted in Smad1/5/8 suppression and alleviated high-dose TGF-β1-induced NPC degeneration. Taken together, it was concluded that high-doses of TGF-β1 contributed to the degeneration of NPCs via the upregulation of ALK1 and Smad1/5/8. |
Databáze: | OpenAIRE |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |