Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region

Möbius, Patrick; Preidl, Raimund; Weber, Manuel; Amann, Kerstin; Neukam, Friedrich Wilhelm; Wehrhan, Falk

doi:10.1007/s00066-017-1192-z

Cited by 5 publications

(2 citation statements)

References 51 publications

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“…SOX9 is also involved in fibrotic disorders, in which it is a key transcriptional regulator of genes related to ECM formation [72]. In vivo loss of SOX9 attenuated cardiac fibrosis in response to ischemic injury [73,74], whereas sustained SOX9 expression was associated with experimental fibrosis [75,76]. SOX9 overexpression in cultured rat fibroblasts is involved in renal tubular EMT and ECM aggregation via the PI3K/AKT signaling pathway [76].…”

Section: Discussionmentioning

confidence: 99%

Type IV Collagen and SOX9 Are Molecular Targets of BET Inhibition in Experimental Glomerulosclerosis

Morgado‐Pascual

Suárez-Álvarez

Marchant

et al. 2022

IJMS

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Progressive glomerulonephritis (GN) is characterized by an excessive accumulation of extracellular (ECM) proteins, mainly type IV collagen (COLIV), in the glomerulus leading to glomerulosclerosis. The current therapeutic approach to GN is suboptimal. Epigenetic drugs could be novel therapeutic options for human disease. Among these drugs, bromodomain and extra-terminal domain (BET) inhibitors (iBETs) have shown beneficial effects in experimental kidney disease and fibrotic disorders. Sex-determining region Y-box 9 (SOX9) is a transcription factor involved in regulating proliferation, migration, and regeneration, but its role in kidney fibrosis is still unclear. We investigated whether iBETs could regulate ECM accumulation in experimental GN and evaluated the role of SOX9 in this process. For this purpose, we tested the iBET JQ1 in mice with anti-glomerular basement membrane nephritis induced by nephrotoxic serum (NTS). In NTS-injected mice, JQ1 treatment reduced glomerular ECM deposition, mainly by inhibiting glomerular COLIV accumulation and Col4a3 gene overexpression. Moreover, chromatin immunoprecipitation assays demonstrated that JQ1 inhibited the recruitment and binding of BRD4 to the Col4a3 promoter and reduced its transcription. Active SOX9 was found in the nuclei of glomerular cells of NTS-injured kidneys, mainly in COLIV-stained regions. JQ1 treatment blocked SOX9 nuclear translocation in injured kidneys. Moreover, in vitro JQ1 blocked TGF-β1-induced SOX9 activation and ECM production in cultured mesangial cells. Additionally, SOX9 gene silencing inhibited ECM production, including COLIV production. Our results demonstrated that JQ1 inhibited SOX9/COLIV, to reduce experimental glomerulosclerosis, supporting further research of iBET as a potential therapeutic option in progressive glomerulosclerosis.

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Section: Discussionmentioning

confidence: 99%

Type IV Collagen and SOX9 Are Molecular Targets of BET Inhibition in Experimental Glomerulosclerosis

Morgado‐Pascual

Suárez-Álvarez

Marchant

et al. 2022

IJMS

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“…A previous study provided that miR-210 regulated cell proliferation by targeting HOXA1 [29]. HOXA9 was shown to be a participator in tissue remodeling of tumors at head or neck, which was mostly changed in solid tumors [33, 34]. In hypoxic pancreatic cancer cells, overexpressed miR-210 was coupled with HOXA9 knockdown, improving cancer cell invasion and migration and enhancing cell resistance to the chemotherapeutic medication [35].…”

Section: Discussion/conclusionmentioning

confidence: 99%

Silencing microRNA-210 in Hypoxia-Induced HUVEC-Derived Extracellular Vesicles Inhibits Hemangioma

Tao

Huang

2020

Cerebrovasc Dis

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Background: Hemangioma (Hem) is a benign tumor commonly seen in infancy with a relative high morbidity. Human umbilical vein endothelial cell (HUVEC)-derived extracellular vesicles (EVs) are actively participated in Hem. Therefore, this study is designed to figure out the underlying mechanism of HUVEC-derived EVs in Hem. Methods: Initially, EVs were separated from HUVECs and identified. HUVEC-derived EVs in normoxia or hypoxia were then cultivated with Hem endothelial cells (HemECs) to test the proliferation, apoptosis, and migration of HemECs. Microarray analysis was performed to select microRNAs (miRs) with differential expression. miR-210 in hypoxia-induced HUVECs was silenced, and the relevant EVs were extracted and then co-cultured with HemECs to perform biological effect experiments. Then, the target relation between miR-210 and homeobox A9 (HOXA9) was identified by the dual luciferase reporter gene assay and RNA immunoprecipitation assay. Moreover, xenograft transplantation was also applied to confirm the in vitro experiments. Results: Hypoxia-induced HUVECs promoted release of EVs, which were absorbed by HemECs. Hypoxia-induced HUVEC-EVs promoted HemEC proliferation and migration and inhibited apoptosis. miR-210 from the hypoxia-induced HUVEC-EVs was highly expressed and promoted HemEC growth. Silencing miR-210 expression in the hypoxia-induced HUVEC-EVs suppresses Hem development in vivo. In addition, miR-210 targeted HOXA9. Conclusion: Silencing miR-210 in HUVEC-derived EVs could suppress Hem by targeting HOXA9. This investigation may provide novel insights for Hem treatment.

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Long-term endothelial dysfunction in irradiated vessels: an immunohistochemical analysis

et al. 2018

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Re-expression of pro-fibrotic, embryonic preserved mediators in irradiated arterial vessels of the head and neck region

Cited by 5 publications

References 51 publications

Type IV Collagen and SOX9 Are Molecular Targets of BET Inhibition in Experimental Glomerulosclerosis

Type IV Collagen and SOX9 Are Molecular Targets of BET Inhibition in Experimental Glomerulosclerosis

Silencing microRNA-210 in Hypoxia-Induced HUVEC-Derived Extracellular Vesicles Inhibits Hemangioma

Long-term endothelial dysfunction in irradiated vessels: an immunohistochemical analysis

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