0

TGF-β Synergizes With ML264 to Block IL-1β-induced Matrix Degradation Mediated by Krüppel-like Factor 5 in the Nucleus Pulposus

Ziang Xie, Zhiwei Jie, Gangliang Wang, Xuewu Sun, Pan Tang, Shuai Chen, An Qin, Jian Wang, Shunwu Fan

Biochim Biophys Acta Mol Basis Dis. 2018 Feb;1864(2):579-589.

PMID: 29196238

Abstract:

Intervertebral disc degeneration causes low back pain.Interleukin-1β (IL-1β) is a well-known inflammatory mediator that is involved in disc degeneration but its molecular mechanisms on catabolic and anabolic events in nucleus pulposus (NP) cells remain unclear. Krüppel-like factor 5 (KLF5) is associated with inflammation and was previously shown to cause cartilage degradation. In this study, we revealed that KLF5 is involved in IL-1β activated NF-kB cascade by enhancing both p65 phosphorylation and p65 acetylation. Moreover, the catabolic effect of KLF5 can be abolished by transforming growth factor-β (TGF-β) via promoting the proteasomal degradation of KLF5. Therefore, a KLF5 inhibitor ML264 was further proved to synergize with TGF-β to attenuate IL-1β-induced intervertebral disc degeneration. These results indicate the critical role of KLF5 in regulating intervertebral disc metabolism and suggest KLF5 inhibitor such as ML264 as potential compound for treatment of degenerative disc disease.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP1550008553 ML264 ML264 1550008-55-3 Price
qrcode

We use cookies to understand how you use our site and to improve the overall user experience. This includes personalizing content and advertising. Read our Privacy Policy

Accept Cookies
x