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

Wu, Xinghuo; Wang, Kun; Hua, Wenbin; Li, Shuai; Liu, Xianzhe; Song, Yu; Zhang, Yukun; Shao, Zengwu; Li, Suyun; Cao, Yang

doi:10.1002/jor.24169

Cited by 6 publications

(4 citation statements)

References 33 publications

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“…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].…”

Section: Involvement Of the Itga2/pi3k/akt Pathway In The Cyclic Mechmentioning

confidence: 99%

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

Wang

Chen

Cao

et al. 2021

Oxidative Medicine and Cellular Longevity

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Background. Intervertebral disc degeneration (IVDD) is one of the major causes of low back pain and motor deficiency. Nucleus pulposus (NP) degeneration plays a key role in the process of IVDD. The mechanical and biological interactions involved in NP degeneration have not been elucidated. The present study is aimed at investigating the effect and mechanism of cyclic mechanical stretch in regulating the function and degeneration of NP cells. Methods. NP cells were subjected to cyclic tensile stress (10% deformation) of 0.1 Hz for 8640 cycles. Cell proliferation was conducted through the MTT assay. The cell cycle and apoptosis were detected by flow cytometry. A gene expression profile chip was used to analyze the differentially expressed genes between the tensile stress group and the control group. Enrichment analysis of Gene Ontology (GO) annotation and signaling pathways were analyzed. Western blot and RNA interference were carried out to investigate the role of the ITGA2/PI3K/AKT pathway in the effect of cyclic mechanical stretch on NP cells. Results. NP cells exhibited a greater ( P < 0.05 ) growth rate in the tensile stress group compared to the control group. Cyclic mechanical stress significantly promoted the cell cycle transition of NP cells from the S phase to the G2/M phase. A fewer proportion of apoptotic cells were found in the tensile stress group ( P < 0.05 ), indicating that cyclic mechanical stretch inhibits NP cell apoptosis. Microarray analysis revealed 689 significant differentially expressed genes between the two groups ( P < 0.05 ), of which 333 genes were upregulated and another 356 genes were downregulated. Cyclic mechanical stretch altered the expression of 31 genes involved in the ITGA2/PI3K/AKT pathway and remarkably promoted this pathway in NP cells. Downregulation of ITGA2 and AKT further demonstrated that the PI3K/AKT pathway was responsible for the proliferation and COL2A1 expression of NP cells upon cyclic mechanical stretch. Conclusions. Cyclic mechanical stretch promoted the proliferation and cell cycle and reversely inhibited the apoptosis of NP cells. Cyclic mechanical stretch promoted COL2A1 expression and ameliorated the degeneration of NP cells via regulation of the ITGA2/PI3K/AKT signaling pathway. Our results may provide a potential target and a possibility of IVDD disease treatment by ameliorating the degenerative changes.

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Section: Involvement Of the Itga2/pi3k/akt Pathway In The Cyclic Mechmentioning

confidence: 99%

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

Wang

Chen

Cao

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…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].…”

Section: гастроэнтерология том 19 № 7 (2020) | | введениеunclassified

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

Lesko¹,

Scientific²,

Варванина³

et al. 2020

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Study Objective: to search for novel approaches to non-invasive diagnosis of pancreatic fibrosis in chronic pancreatitis (CP) patients. Study Design: prospective comparative non-randomised study. Materials and Methods. 43 subjects were examined: 22 (51.2%) patients with calcific CP and 21 (48.8%) patients with CP resulting from acute pancreatitis with pancreonecrosis, aged 35 to 82 years old. All patients underwent multislice computer-aided tomography (CT) of abdomen with IV contrast, and had their fibronectin (FN), С-peptide and faecal pancreatic elastase 1 concentrations measured. Study Results. There were no differences in C-peptide between study groups (p = 0,18). Faecal elastase 1 concentration (108.36 ± 144 μg/g) was significantly lower in calcific CP (p = 0.03) vs. patients with post-pancreonecrosis CP (185.67 ± 145.1 μg/g). Blood FN level negatively correlated with CP severity (M-ANNHEIM system) (r = –0.36, p = 0.018). In calcific CP, median contrast ratio (1.01 ± 0.06) was significantly higher (p = 0.033) than in post-pancreonecrosis CP (0.95 ± 0.14). Conclusion. Patients with calcific CP demonstrated more severe exocrine insufficiency. Decreased FN levels in severe CP are likely to be due to long-term increased FN intake because of pacreatic fibrosis. Pancreatic fibrosis augmentation impacts pancreas contrast study and results in higher contrast ratio at CT. Therefore, it allows using this parameter for non-invasive diagnosis of pancreas fibrosis in patients with CP. Keywords: fibrosis, chronic pancreatitis, pancreas, computer-aided tomography.

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“…Integrins constitute an important protein family on the surface of the cell membrane, which mediate cell adhesion, migration and other biological functions (Wu, 2019 ). Our previous study (Gao, 2016 a) demonstrated that integrin α1 regulates ECM mRNA synthesis and NP cell migration under PMS.…”

Section: Introductionmentioning

confidence: 99%

Effects of periodic mechanical stress on cytoskeleton dependent lipid raft-induced integrin ɑ1 activation in rat nucleus pulposus cells

Gao

Chen

et al. 2023

J Mol Histol

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Extracellular matrix (ECM) production and nucleus pulposus (NP) cell migration increase under periodic mechanical stress (PMS), but the underpinning regulatory mechanism remains unclear. This work aimed to examine the regulatory effects of cytoskeleton-lipid raft-integrin α1 signaling in NP cells exposed to PMS. Briefly, In NP cells, cytoskeleton rearrangement, lipid raft aggregation and integrin α1 expression in the stress and control groups were assessed by immunofluorescent staining and immunoblot. In addition, cell migration and ECM gene expression were detected by a scratch test and quantitative reverse transcription polymerase chain reaction (qRT‑PCR), respectively. As a result, PMS up-regulated ECM gene expression and enhanced NP cell migration (both P < 0.05), accompanied by increased integrin α1, lipid raft, caveolin-3, F-actin and β-tubulin amounts. Pretreatment with the lipid raft inhibitor methyl-β-cyclodextrin (MβCD) or small interfering RNA (siRNA) targeting caveolin-3 resulted in decreased ECM mRNA synthesis and cell migration induced by PMS (both P < 0.05); meanwhile, integrin α1 expression was also reduced. F-actin and β-tubulin inhibition by cytochalasin D and colchicine, respectively, not only reduced ECM mRNA synthesis and cell migration (both P < 0.05), but also disrupted lipid raft and caveolin-3 amount increases induced by PMS in NP cells. In conclusion, PMS promotes ECM mRNA up-regulation and cell migration through the cytoskeleton-lipid raft-integrin α1 signaling pathway, inhibiting cytoskeleton and lipid rafts could block the cellular effects.

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

Cited by 6 publications

References 33 publications

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

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

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

Effects of periodic mechanical stress on cytoskeleton dependent lipid raft-induced integrin ɑ1 activation in rat nucleus pulposus cells

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