ArticleMatrix biology : journal of the International Society for Matrix Biology2019
RNA binding protein HuR regulates extracellular matrix gene expression and pH homeostasis independent of controlling HIF-1α signaling in nucleus pulposus cells.
Article in Matrix biology : journal of the International Society for Matrix Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Transcriptome-wide splicing analysis reveals HuR-regulated post-transcriptional programs in osteocytes.iScience · 2026Article
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- In Vitro Anti-Aging Effects of Yeast/Rice Fermentation Filtrate Combined with Sialic Acid in Cosmetic Applications.Antioxidants (Basel, Switzerland) · 2025Article
- Article
- PPIH as a poor prognostic factor increases cell proliferation and m6A RNA methylation in hepatocellular carcinoma.American journal of cancer research · 2024Article
- Emerging roles of RNA binding proteins in intervertebral disc degeneration and osteoarthritis.Orthopaedic surgery · 2023Review
- Hypoxic Effects on Matrix Metalloproteinases' Expression in the Tumor Microenvironment and Therapeutic Perspectives.International journal of molecular sciences · 2023Review
- Regulation of Ion Homeostasis for Enhanced Tumor Radio-Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- A review of Duhuo Jisheng decoction mechanisms in intervertebral disc degeneration in vitro and animal studies.Journal of orthopaedic surgery and research · 2023Review
- Exosomal circSPIRE1 mediates glycosylation of E-cadherin to suppress metastasis of renal cell carcinoma.Oncogene · 2023Article
- MYB sustains hypoxic survival of pancreatic cancer cells by facilitating metabolic reprogramming.EMBO reports · 2023Article
- SOX2 Promotes Invasion in Human Bladder Cancers through MMP2 Upregulation and FOXO1 Downregulation.International journal of molecular sciences · 2022Article
- m6A hypomethylation of DNMT3B regulated by ALKBH5 promotes intervertebral disc degeneration via E4F1 deficiency.Clinical and translational medicine · 2022Article
- The role of HIF proteins in maintaining the metabolic health of the intervertebral disc.Nature reviews. Rheumatology · 2021Review
- Role of autophagy in intervertebral disc and cartilage function: implications in health and disease.Matrix biology : journal of the International Society for Matrix Biology · 2021Review
- RNA-binding protein HuR suppresses senescence through Atg7 mediated autophagy activation in diabetic intervertebral disc degeneration.Cell proliferation · 2021Article
- Elavl1 Impacts Osteogenic Differentiation and mRNA Levels of Genes Involved in ECM Organization.Frontiers in cell and developmental biology · 2021Article
- Sox9 deletion causes severe intervertebral disc degeneration characterized by apoptosis, matrix remodeling, and compartment-specific transcriptomic changes.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
- Alterations in ECM signature underscore multiple sub-phenotypes of intervertebral disc degeneration.Matrix biology plus · 2020Article
- TonEBP-deficiency accelerates intervertebral disc degeneration underscored by matrix remodeling, cytoskeletal rearrangements, and changes in proinflammatory gene expression.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Nucleus pulposus (NP) cells reside in the hypoxic niche of the intervertebral disc. Studies have demonstrated that RNA-binding protein HuR modulates hypoxic signaling in several cancers, however, its function in the disc is unknown. HuR did not show cytoplasmic translocation in hypoxia and its silencing did not alter levels of Hif-1α or HIF-targets in NP cells. RNA-Sequencing data revealed that important extracellular matrix-related genes including several collagens, MMPs, aggrecan, Tgf-β3 and Sdc4 were regulated by HuR. Further analysis of HuR-silenced NP cells confirmed that HuR maintained expression of these matrix genes. We confirmed decreased levels of secreted collagen I and Sdc4 and increased pro-MMP13 in HuR-knockdown cells. In addition, messenger ribonucleoprotein immunoprecipitation demonstrated HuR binding to Tgf-β3 and Sdc4 mRNAs. Interestingly, while HuR bound to Hif-1α and Vegf mRNAs, it was clear that compensatory mechanisms sustained their expression when HuR was silenced. Noteworthy, despite the presence of multiple HuR-binding sites and reported interaction in other cell types, HuR showed no binding to Pgk1, Eno1, Pdk1 and Pfkfb3 in NP cells. Metabolic studies showed a significant decrease in the extracellular acidification rate (ECAR) and mitochondrial oxygen consumption rate (OCR) and acidic pH in HuR-silenced NP cells, without appreciable change in total OCR. These changes were likely due to decreased Ca12 expression in HuR silenced cells. Taken together, our study demonstrates for the first time that HuR regulates extracellular matrix (ECM) and pH homeostasis of NP cells and has important implications in the maintenance of intervertebral disc health.
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