FSTL1 Accelerates Nucleus Pulposus Cell Senescence and Intervertebral Disc Degeneration Through TLR4/NF-κB Pathway

Yan, Xu; Ding, Jing-Yu; Zhang, Ren-Jie; Zhang, Hua-Qing; Kang, Liang; Jia, Chong-Yu; Liu, Xiao-Ying; Shen, Cai-Liang

doi:10.1007/s10753-024-01972-0

Cited by 5 publications

(3 citation statements)

References 46 publications

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“…In addition, FSTL1 increases with age in the NP of mice, and heterozygous FSTL1 knockout mice exhibit a reduced degree of degeneration compared with wild-type mice in a mouse model of IDD [ 104 ]. More recently, Yan and colleagues reported that the expression levels of FSTL1 are positively correlated with the disease severity of human IDD [ 39 ]. Mechanistically, recombinant human FSTL1 directly induces cellular senescence, accompanied by upregulated expression of proinflammatory SASP factors in NP cells derived from human IDD tissue [ 39 ].…”

Section: Matricellular Proteins In Cellular Senescencementioning

confidence: 99%

“…More recently, Yan and colleagues reported that the expression levels of FSTL1 are positively correlated with the disease severity of human IDD [ 39 ]. Mechanistically, recombinant human FSTL1 directly induces cellular senescence, accompanied by upregulated expression of proinflammatory SASP factors in NP cells derived from human IDD tissue [ 39 ]. In addition, FSTL1 silencing by siRNA ameliorates IDD progression and decreases the numbers of p16- and IL-1β-positive cells in the rabbit IDD model [ 39 ].…”

Section: Matricellular Proteins In Cellular Senescencementioning

confidence: 99%

“…Mechanistically, recombinant human FSTL1 directly induces cellular senescence, accompanied by upregulated expression of proinflammatory SASP factors in NP cells derived from human IDD tissue [ 39 ]. In addition, FSTL1 silencing by siRNA ameliorates IDD progression and decreases the numbers of p16- and IL-1β-positive cells in the rabbit IDD model [ 39 ]. Taken together, targeting of FSTL1-induced senescence might be a novel therapeutic strategy for IDD.…”

Section: Matricellular Proteins In Cellular Senescencementioning

confidence: 99%

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Involvement of Matricellular Proteins in Cellular Senescence: Potential Therapeutic Targets for Age-Related Diseases

Fujita,

Sasada,

Iyoda

et al. 2024

IJMS

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Senescence is a physiological and pathological cellular program triggered by various types of cellular stress. Senescent cells exhibit multiple characteristic changes. Among them, the characteristic flattened and enlarged morphology exhibited in senescent cells is observed regardless of the stimuli causing the senescence. Several studies have provided important insights into pro-adhesive properties of cellular senescence, suggesting that cell adhesion to the extracellular matrix (ECM), which is involved in characteristic morphological changes, may play pivotal roles in cellular senescence. Matricellular proteins, a group of structurally unrelated ECM molecules that are secreted into the extracellular environment, have the unique ability to control cell adhesion to the ECM by binding to cell adhesion receptors, including integrins. Recent reports have certified that matricellular proteins are closely involved in cellular senescence. Through this biological function, matricellular proteins are thought to play important roles in the pathogenesis of age-related diseases, including fibrosis, osteoarthritis, intervertebral disc degeneration, atherosclerosis, and cancer. This review outlines recent studies on the role of matricellular proteins in inducing cellular senescence. We highlight the role of integrin-mediated signaling in inducing cellular senescence and provide new therapeutic options for age-related diseases targeting matricellular proteins and integrins.

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Section: Matricellular Proteins In Cellular Senescencementioning

confidence: 99%

Section: Matricellular Proteins In Cellular Senescencementioning

confidence: 99%

Section: Matricellular Proteins In Cellular Senescencementioning

confidence: 99%

See 1 more Smart Citation

Involvement of Matricellular Proteins in Cellular Senescence: Potential Therapeutic Targets for Age-Related Diseases

Fujita,

Sasada,

Iyoda

et al. 2024

IJMS

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Nordihydroguaiaretic acid suppresses ferroptosis and mitigates intervertebral disc degeneration through the NRF2/GPX4 axis

Zhang,

Li,

Chen

et al. 2024

International Immunopharmacology

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FSTL1 and TLR4 interact with PEDV structural proteins to promote virus adsorption to host cells

Liu,

Kong,

Liu

et al. 2024

J Virol

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Infection with porcine epidemic diarrhea virus (PEDV) results in enormous economic damage to the global swine industry. PEDV starts its life cycle by binding to the receptors of host cells and adsorbing onto the cellular surfaces. However, it is still unknown how PEDV adsorbs onto the surface of host cells and the mechanism beneath the interplay of host cell transmembrane protein with PEDV proteins. FSTL1, which is a secreted glycoprotein, participates in diverse pathological and physiological processes, including immune modulation and cell proliferation and differentiation. The transmembrane protein, TLR4, serves as a pattern recognition receptor recognizing a broad spectrum of pathogens, which exerts a crucial effect on the host immune system. In this study, we identified that FSTL1 promoted PEDV infection. Further studies demonstrated the interactive relationship between FSTL1 and PEDV structural proteins (N and S2). In addition, we also confirmed that TLR4 interacted with FSTL1 and PEDV N, S1, and S2 proteins on the cell surface. Moreover, FSTL1 promoted the interaction of TLR4 and PEDV and induced viral adsorption to host cells. This study offers explicit evidence that FSTL1 and TLR4 act as mediators for host cell adsorption of PEDV by interacting with PEDV N/S proteins. IMPORTANCE As a highly infectious porcine epidemic diarrhea virus (PEDV)-induced intestinal condition of swine, porcine epidemic diarrhea (PED) results in a 100% death rate among suckling piglets and poses a serious economic burden to global swine farming. Therefore, it is essential to investigate the mechanism of virus infection, replication, and proliferation. Virus begins its life cycle by binding to the receptor of host cells and adsorbing onto the cellular surfaces. However, it remains unclear how PEDV adsorbs onto the host cell surfaces. This study revealed that host protein FSTL1 interacted with the PEDV N and S2 proteins, while TLR4 interacted with the FSTL1 and PEDV proteins (N, S1, and S2). Moreover, we thoroughly and methodically demonstrated that FSTL1 was engaged in the PEDV internalization and attachment processes by promoting the recognition of PEDV N\S proteins by TLR4 and induced the viral adsorption to host cells.

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FSTL1 Accelerates Nucleus Pulposus Cell Senescence and Intervertebral Disc Degeneration Through TLR4/NF-κB Pathway

Cited by 5 publications

References 46 publications

Involvement of Matricellular Proteins in Cellular Senescence: Potential Therapeutic Targets for Age-Related Diseases

Involvement of Matricellular Proteins in Cellular Senescence: Potential Therapeutic Targets for Age-Related Diseases

Nordihydroguaiaretic acid suppresses ferroptosis and mitigates intervertebral disc degeneration through the NRF2/GPX4 axis

FSTL1 and TLR4 interact with PEDV structural proteins to promote virus adsorption to host cells

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