ArticleFrontiers in pharmacology2018
Rapamycin Upregulates Connective Tissue Growth Factor Expression in Hepatic Progenitor Cells Through TGF-β-Smad2 Dependent Signaling.
Article in Frontiers in pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Radiotherapy and cytokines: A systems view of immunotherapy and toxicity (Review).International journal of molecular medicine · 2026Review
- Mechanisms underlying persistent liver fibrosis progression in Schistosoma-infected individuals post-treatment.Infectious diseases of poverty · 2025Article
- Review
- Article
- Rapamycin Inhibits Senescence and Improves Immunomodulatory Function of Mesenchymal Stem Cells Through IL-8 and TGF-β Signaling.Stem cell reviews and reports · 2024Article
- TGF-β, IL-1β, IL-6 levels and TGF-β/Smad pathway reactivity regulate the link between allergic diseases, cancer risk, and metabolic dysregulations.Frontiers in immunology · 2024Article
- Decoding of translation-regulating entities reveals heterogeneous translation deficiency patterns in cellular senescence.Aging cell · 2023Article
- Collagen I-DDR1 signaling promotes hepatocellular carcinoma cell stemness via Hippo signaling repression.Cell death and differentiation · 2023Article
- A myeloid leukemia factor homolog is involved in tolerance to stresses and stress-induced protein metabolism in Giardia lamblia.Biology direct · 2023Article
- Radiation-induced liver disease: beyond DNA damage.Cell cycle (Georgetown, Tex.) · 2023Review
- Kinsenoside Protects Against Radiation-Induced Liver FibrosisFrontiers in pharmacology · 2022Article
- Mass spectrometric investigations of caloric restriction mimetics.Proteomics · 2021Review
- Rapamycin Protects Skin Fibroblasts From UVA-Induced Photoaging by Inhibition of p53 and Phosphorylated HSP27.Frontiers in cell and developmental biology · 2021Article
- Insulin-Like Growth Factor Binding Protein-Related Protein 1 Activates Primary Hepatic Stellate Cells via Autophagy Regulated by the PI3K/Akt/mTOR Signaling Pathway.Digestive diseases and sciences · 2020Article
- Review
- Effects of high glucose on proliferation and function of circulating fibrocytes: Involvement of CXCR4/SDF‑1 axis.International journal of molecular medicine · 2019Article
- DEPTOR induces a partial epithelial-to-mesenchymal transition and metastasis via autocrine TGFβ1 signaling and is associated with poor prognosis in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2019Article
- [Rapamycin alleviates inflammation by up-regulating TGF-β/Smad signaling in a mouse model of autoimmune encephalomyelitis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2019Article
- 6-Bromoindirubin-3'-Oxime (6BIO) Suppresses the mTOR Pathway, Promotes Autophagy, and Exerts Anti-aging Effects in Rodent Liver.Frontiers in pharmacology · 2019Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rapamycin (sirolimus) is a mTOR kinase inhibitor and is widely used as an immunosuppressive drug to prevent graft rejection in organ transplantation currently. However, some recent investigations have reported that it had profibrotic effect in the progression of organ fibrosis, and its precise role in the liver fibrosis is still poorly understood. Here we showed that rapamycin upregulated connective tissue growth factor (CTGF) expression at the transcriptional level in hepatic progenitor cells (HPCs). Using lentivirus-mediated small hairpin RNA (shRNA) we demonstrated that knockdown of mTOR, Raptor, or Rictor mimicked the effect of rapamycin treatment. Mechanistically, inhibition of mTOR activity with rapamycin resulted in a hyperactive PI3K-Akt pathway, whereas this activation inhibited the expression of CTGF in HPCs. Besides, rapamycin activated the TGF-β-Smad signaling, and TGF-β receptor type I (TGFβRI) serine/threonine kinase inhibitors completely blocked the effects of rapamycin on HPCs. Moreover, Smad2 was involved in the induction of CTGF through rapamycin-activated TGF-β-Smad signaling as knockdown completely blocked CTGF induction, while knockdown of Smad4 expression partially inhibited induction, whereas Smad3 knockdown had no effect. Rapamycin also induced ROS generation and latent TGF-β activation which contributed to TGF-β-Smad signaling. In conclusion, this study demonstrates that rapamycin upregulates CTGF in HPCs and suggests that rapamycin has potential fibrotic effect in liver.
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