ArticlePloS one2013
IL-6 regulates Mcl-1L expression through the JAK/PI3K/Akt/CREB signaling pathway in hepatocytes: implication of an anti-apoptotic role during liver regeneration.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
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- Immunological mechanisms and emerging therapeutic targets in alcohol-associated liver disease.Cellular & molecular immunology · 2025Review
- Epigenetic modifications in the murine liver upon depletion of transcriptional coregulator host cell factor 1.BMC genomics · 2025Article
- The HCV-Melanoma Paradox: First Multi-Cohort and Molecular Net-Work Analysis Reveals Lower Incidence but Worse Outcomes-Integrating Clinical, Real-World, and In Silico Data.Medicina (Kaunas, Lithuania) · 2024Article
- Role of the portal system in liver regeneration: From molecular mechanisms to clinical management.Liver research (Beijing, China) · 2024Review
- Novel insights: crosstalk with non-puerperal mastitis and immunity.Frontiers in immunology · 2024Review
- Intestinal Microbiotas and Alcoholic Hepatitis: Pathogenesis and Therapeutic Value.International journal of molecular sciences · 2023Review
- Article
- The role of gut microbiota in liver regeneration.Frontiers in immunology · 2022Review
- Sensitization effect of kaempferol from persimmon leaves on HepG2 hepatoma cells with ABT-199 resistance and its molecular mechanisms.Frontiers in pharmacology · 2022Article
- The two facets of gp130 signalling in liver tumorigenesis.Seminars in immunopathology · 2021Review
- Focused screening reveals functional effects of microRNAs differentially expressed in colorectal cancer.BMC cancer · 2019Article
- The Two-Faced Cytokine IL-6 in Host Defense and Diseases.International journal of molecular sciences · 2018Review
- The Role of Adipokines in Surgical Procedures Requiring Both Liver Regeneration and Vascular Occlusion.International journal of molecular sciences · 2018Review
- Musashi-1 regulates AKT-derived IL-6 autocrinal/paracrinal malignancy and chemoresistance in glioblastoma.Oncotarget · 2016Article
- MICU1 regulation of mitochondrial Ca(2+) uptake dictates survival and tissue regeneration.Nature communications · 2016Article
- Characterization of adipose-derived stem cells from subcutaneous and visceral adipose tissues and their function in breast cancer cells.Oncotarget · 2015Article
- Accounting for the delay in the transition from acute to chronic pain: axonal and nuclear mechanisms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- C/EBPα inhibits proliferation of breast cancer cells via a novel pathway of miR-134/CREB.International journal of clinical and experimental pathology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo investigate the role and the regulation of the long variant of myeloid cell leukemia-1 protein (Mcl-1L) during liver regeneration.
backgroundLiver regeneration is an important phenomenon after liver injury. The rat partial hepatectomy (PH) model was used to characterize liver regeneration and Mcl-1L expression after PH.
methodsMale Wistar rats were subjected to 70% PH. The expression of mcl-1L mRNA was determined by quantitative RT-PCR, and protein levels were analyzed by Western blot analysis and immunohistochemistry during liver regeneration. Functional evaluations of Mcl-1L were tested using chemical inhibition (flavopiridol), genetic inhibition (siRNA) of Mcl-1L production, and by assaying for annexin V levels and DNA ladder formation. Serum IL-6 levels were determined by enzyme immunoassays; signal transduction of IL-6-regulated Mcl-1L expression was verified by chemical inhibitors and decoy double-stranded oligodeoxynucleotides.
resultsHigh levels of Mcl-1L were observed in remnant tissue at 4 h after PH. Administration of flavopiridol decreased Mcl-1L accumulation and also inhibited liver regeneration. IL-6 administration promoted the accumulation of Mcl-1L in rat hepatocytes, an effect that was impaired by siRNA treatments that reduced Mcl-1L production. Chemical inhibition and decoy oligonucleotide competition demonstrated that IL-6-induced Mcl-1L production required signaling mediated by JAK kinase, phosphoinositide 3-kinase (PI3K), and cAMP response-element-binding (CREB) proteins.
conclusionMcl-1L is an anti-apoptotic protein induced during liver regeneration after PH in rats. The expression of Mcl-1L is induced by IL-6 through the JAK/PI3K/Akt/CREB signaling pathway. Chemotherapy drugs that depend on Mcl-1L- or IL-6-related signaling should be considered carefully before use in patients undergoing hepatectomy for malignant tumor resection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.