Dysregulation of YAP by the Hippo pathway is concerned in intervertebral disc degeneration, cell contact inhibition, and cell senescence.
Oncotarget. 2018 Jan 05;9(2):2175-2192
Authors: Zhang C, Wang F, Xie Z, Chen L, Sinkemani A, Yu H, Wang Ok, Mao L, Wu X
The Hippo pathway performs vital roles in wound therapeutic, tissue restore and regeneration, and within the remedy of degenerative illnesses, by regulating cell proliferation and apoptosis in mammals. Intervertebral disc degeneration (IDD) is likely one of the main causes of low again ache, a widespread concern related to a heavy financial burden. Nevertheless, the mechanism underlying how the Hippo pathway regulates IDD just isn’t effectively understood. Right here, we exhibit that the Hippo pathway is concerned in pure IDD. Activation and dephosphorylation of yes-associated protein (YAP) had been noticed in youthful rat discs, and decreased steadily with age. Surprisingly, Hippo pathway suppression was accompanied by overexpression of YAP, attributable to acute disc damage, suggesting a restricted skill for self-repair in IDD. We additionally demonstrated that YAP is inhibited by cell-to-cell contact through the Hippo pathway in vitro. Phosphorylation by massive tumor suppressor kinases 1/2 (LATS1/2) led to cytoplasmic translocation and inactivation of YAP. YAP dephosphorylation was primarily localized within the nucleus and controlled by the Hippo pathway, whereas YAP dephosphorylation occurred within the cytoplasm and was related to nucleus pulposus cell (NPC) senescence. Furthermore, NPCs had been transfected with shYAP and it accelerates the untimely senescence of cells by interfered Hippo pathway by YAP. Subsequently, our outcomes point out that the Hippo pathway performs an vital function in sustaining the homeostasis of intervertebral discs and controlling NPC proliferation.
PMID: 29416763 [PubMed]