The Role of Smad2 in Transforming Growth Factor β1–Induced Hypertrophy of Ligamentum Flavum

Wang, Lianlei; Chang, Mingzheng; Tian, Yonghao; Jiang, Yan; Xu, Weijuan; Yuan, Suomao; Zhang, Kai; Liu, Xinyu

doi:10.1016/j.wneu.2021.03.147

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…Patients with lumbar spinal stenosis have hypertrophic ligamentum flavum cells, and SIRT6 promotes telomerase activity to prevent DNA damage and senescence ( Chen et al, 2021 ). Fibrillogenic activity is mediated by TGFβ-1 through the Smad proteins, and we have observed that Smad2 knockdown influences the TGFβ-1signaling pathway by lowering TGFβ-1 levels ( Wang et al, 2021 ). The role of the p38 mitogen-activated protein kinase (MAPK) signaling pathway in developing human lumbar LFH is mediated by transforming growth factor 1 (TGF1/connective tissue growth factor) ( Lu et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Immune cell infiltration and the genes associated with ligamentum flavum hypertrophy: Identification and validation

Duan

Zhao

et al. 2022

Front. Cell Dev. Biol.

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Ligamentum flavum hypertrophy (LFH) is a common cause of spinal stenosis. The aim of the current study was to identify the differentially expressed genes (DEGs) in LFH and the molecular mechanisms underlying the development of and immune responses to LFH. The gene expression omnibus (GEO) database was used to obtain the GSE113212 dataset, and the DEGs were derived from microarray data. To identify critical genes and signaling pathways, gene ontology enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network analyses were performed, followed by immune cell infiltration and Friends analyses using the retrieved datasets. The results were validated using quantitative real-time PCR. The 1530 DEGs identified comprised 971 upregulated and 559 downregulated genes. KEGG analysis revealed that DEGs were mostly enriched in the PI3K-Akt signaling pathway, while PPI network analysis identified tumor necrosis factor, interleukin (IL)-6, IL-10, epidermal growth factor receptor, and leptin as important nodes, which was validated by qPCR and IHC in human LFH tissues in vitro. A significant positive correlation was found between key LFH immune-related DEGs and several immune cell types, including T and B cells. The findings of the present study might lead to novel therapeutic targets and clinical approaches, as they provide insights into the molecular mechanisms of LFH.

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Section: Introductionmentioning

confidence: 99%

Immune cell infiltration and the genes associated with ligamentum flavum hypertrophy: Identification and validation

Duan

Zhao

et al. 2022

Front. Cell Dev. Biol.

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“…Theoretically, MIF also can affect the fibroblasts of LF. Furthermore, TGFβ1, one of the most closely related factors to LF hypertrophy, can not only promote the proliferation of fibroblasts but also contribute to the COL-1 and COL-3 collagen fibers in LF ( 8 ). MMP has the function of dissociating the extracellular matrix ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

“…Inflammatory factors serve a vital role in the hypertrophy process of LF ( 7 ). TGFβ1 can significantly promote the proliferation of LF fibroblasts and the overexpression of collagen fibers, while MMP13 has a distinct function of elastic fiber degradation in the LF extracellular matrix ( 8 , 9 ). A connection exists between macrophage migration inhibitory factor [MIF; novoprotein recombinant human MIF (n-6his) (ch33)] and TGFβ1 and MMP ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Macrophage migration inhibitory factor takes part in the lumbar ligamentum flavum hypertrophy

Zheng

et al. 2022

Mol Med Rep

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The present study aimed to observe the content difference of macrophage migration inhibitory factor [MiF; novoprotein recombinant human MiF (n-6his) (ch33)], TGFβ1 and MMP13 in patients with and without ligamentum flavum (lF) hypertrophy and investigate the roles of MiF in lF hypertrophy. The concentration of MiF, TGFβ1 and MMP13 in lF were detected by eliSa in a lumbar spinal stenosis (lSS) group and a lumbar disc herniation (ldH) group. culture of primary lFs and identification were performed for the subsequent study. cell treatments and cell proliferation assay by ccK-8 was performed. Western blot and quantitative Pcr analysis were used to detect the expression of TGFβ1, MMP13, type i collagen (col-1) and type iii collagen (col-3) and Src which were promoted by MiF. The concentration of MiF, TGFβ1 and MMP13 were higher in the lSS group compared with the LDH group. Culture of primary LFs and identification were performed. Significant difference in LFs proliferation occurred with treatment by MiF at a concentration of 40 nM for 48 h (P<0.05). The gene and protein expression of TGFβ1, MMP13, col-1, col-3 and Src were promoted by MiF (P<0.05). Proliferation of lFs was induced by MiF and MiF-induced proliferation of lFs was inhibited by PP1 (a Src inhibitor). MiF may promote the proliferation of lFs through the Src kinase signaling pathway and can promote extracellular matrix changes by its pro-inflammatory effect. MIF and its mediated inflammatory reaction are driving factors of LF hypertrophy.

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“…Another difference of this study from other others in which the role of SMAD-2 was evaluated for various diseases is that SMAD-2 protein and mRNA levels were not examined in tissue but examined in serum. 30,31 However, it should be noted that this study was conducted as an effort to contribute to a potential screen test for BC.…”

Section: Ta B L Ementioning

confidence: 99%

Can serum matrix metalloproteinase‐9 and SMAD‐2 levels predict lamina propria invasion in bladder urothelial carcinoma?

et al. 2021

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Lamina propria (LP) invasion is the determinant of stage progression from Ta to T1 in bladder cancer (BC). It is important because the risk classification, deciding for appropriate adjuvant intravesical therapies, and the frequency of cystoscopic monitoring in non-muscle-invasive bladder cancer (NMIBC) depends on the pathological T stage. 1 Tumour invasion is related to the reconstruction of the connective tissue of the extracellular matrix (ECM). Cell-matrix interactions are regulated by several proteolytic enzymes, such as matrix metalloproteinase-9 (MMP-9), which are responsible for the hydrolysis of ECM components. These enzymes play a key role in the maintenance of the composition and integrity of the ECM structure, monitoring the signals generated by the matrix molecules, cell

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The Role of Smad2 in Transforming Growth Factor β1–Induced Hypertrophy of Ligamentum Flavum

Cited by 6 publications

References 39 publications

Immune cell infiltration and the genes associated with ligamentum flavum hypertrophy: Identification and validation

Immune cell infiltration and the genes associated with ligamentum flavum hypertrophy: Identification and validation

Macrophage migration inhibitory factor takes part in the lumbar ligamentum flavum hypertrophy

Can serum matrix metalloproteinase‐9 and SMAD‐2 levels predict lamina propria invasion in bladder urothelial carcinoma?

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