Fibronectin induced ITGβ1/FAK‐dependent apoptotic pathways determines the fate of degenerative NP cells

Abstract

Intervertebral disc (IVD) degeneration is caused by a decrease in nucleus pulposus (NP) cells, due mainly to apoptosis. Focal adhesion kinase (FAK) is involved in the integrin (ITG)-mediated control of cell adhesion and anoikis (apoptosis). To explore the involvement of ITGb1/FAK-dependent apoptotic pathways in disc degeneration, histological, and molecular biological studies on the protein expression of fibronectin (FN), ITGb1, and syndecan 4 (SYND4) in non-degenerative and degenerative NP tissues were conducted. Degenerative NP cells were isolated and cultured in the presence of SYND4 and/or ITGb1, with or without an FAK inhibitor. The effects of upregulation or knockdown of ITGb1 gene expression were also examined. The TUNEL assay was used to determine the percentage of apoptotic cells. Western blotting was used to detect the expression of SYND4, ITGb1, FAK, and downstream pathway proteins. The results showed that extracellular FN was degraded during the IVD degeneration process, detrimentally affecting the function, and survival of NP cells. The apoptotic rate was increased by ITGb1 activation, but partially reduced by FN. After ITGb1 knockdown, the FAK/PI3 K/AKT axis was activated in the ITGb1/FAK-dependent pathways, resulting in increased cell adherence capacity and decreased anoikis. FN rescued the degenerative NP cells from anoikis through the FAKdependent signaling pathways. In conclusion, the extracellular matrix protein FN is essential for maintaining the function and survival of NP cells through ITGb1/FAK-dependent apoptotic pathways during disc degeneration. ß

Recombinant Laminin-511 Fragment (iMatrix-511) Coating Supports Maintenance of Human Nucleus Pulposus Progenitor Cells In Vitro

“…(Figure 1) The Erk1/2 pathway is a downstream signaling molecule of the mitogen-activated protein kinase signaling cascade, is also known to be involved in the production of inflammatory cytokines, and has been connected with regulating NP cells and ECM-binding [48]. On the other hand, the Akt pathway functions as a switch between cell death and cell survival [49,50]. It has been reported that activation of the Akt pathway in NP cells is involved in the enhancement of cell adhesion and inhibition of apoptosis [49,50].…”

Cyclic Mechanical Stretch Ameliorates the Degeneration of Nucleus Pulposus Cells through Promoting the ITGA2/PI3K/AKT Signaling Pathway

“…Integrin α2β1 participates in the estrogenintervened PI3K/AKT pathway regulating the antiapoptotic effect of intervertebral disc aging and degeneration and participates in FAK/PI3K signaling regulating adherence capacity and anoikis of NP cells in IVD degeneration [30]. The FAK/-PI3K/AKT pathway has been reported to acts as integrindependent signaling in regulating apoptosis of NP cells during the process of disc degeneration [31]. Integrins function synergistically with SYND4, and FAK/PI3K signaling participates in regulating adherence capacity and anoikis of NP cells in IVD degeneration [32].…”

Novel Approaches to Non-invasive Diagnosis of Pancreatic Fibrosis in Chronic Pancreatitis

“…и активации различных сигнальных белков, что приводит к секреции клетками металлопротеиназ и стимуляции их миграции. Это проявляется в ряде физиологических и патологических процессов, включая сепсис, синдром диссеминированного внутрисосудистого свертывания, острые воспалительные заболевания и развитие злокачественных опухолей [11][12][13].…”