ArticleInternational journal of molecular sciences2018
Hypoxia Activates Src and Promotes Endocytosis Which Decreases MMP-2 Activity and Aggravates Renal Interstitial Fibrosis.
Article in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 29 citations in OpenAlex.
- Functional and transcriptional responses of chicken macrophages to hypoxia.Poultry science · 2025Article
- SLC7A11 in Fibrosis: Molecular Mechanisms and Future Prospects.Aging and disease · 2025Review
- Mesenchymal Stem Cell-conditioned Medium Attenuated CoClCurrent pharmaceutical design · 2025Article
- Research progress on miR-124-3p in the field of kidney disease.BMC nephrology · 2024Review
- Mining host candidate regulators of schistosomiasis-induced liver fibrosis in response to artesunate therapy through transcriptomics approach.PLoS neglected tropical diseases · 2023Article
- Podocarpusflavone alleviated renal fibrosis in obstructive nephropathy by inhibiting Fyn/Stat3 signaling pathway.Journal of natural medicines · 2023Article
- Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis.Open life sciences · 2023Article
- Src Family Kinases: A Potential Therapeutic Target for Acute Kidney Injury.Biomolecules · 2022Review
- MiR-1224 downregulation inhibits OGD/R-induced hippocampal neuron apoptosis through targeting Ku protein.Metabolic brain disease · 2022Article
- Role of MMP-2 and CD147 in kidney fibrosis.Open life sciences · 2022Review
- The role of the macrophage-to-myofibroblast transition in renal fibrosis.Frontiers in immunology · 2022Review
- Hypoxic tubular epithelial cells regulate the angiogenesis of HMEC-1 cells via mediation of Rab7/MMP-2 axis.Aging · 2021Article
- Article
- miR‑212 promotes renal interstitial fibrosis by inhibiting hypoxia‑inducible factor 1‑α inhibitor.Molecular medicine reports · 2021Article
- Downregulation of RAB7 and Caveolin-1 increases MMP-2 activity in renal tubular epithelial cells under hypoxic conditions.Open medicine (Warsaw, Poland) · 2021Article
- The Versatile Role of Matrix Metalloproteinase for the Diverse Results of Fibrosis Treatment.Molecules (Basel, Switzerland) · 2019Review
- Modifying a Commonly Expressed Endocytic Receptor Retargets Nanoparticles in Vivo.Nano letters · 2018Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aggravation of renal interstitial fibrosis in the advanced-stage of chronic kidney disease is related to decreased matrix metalloproteinase-2 (MMP-2) activity, which is induced by hypoxia in the kidney; however, the specific mechanism remains unclear. We previously demonstrated that inhibition of Caveolin-1, a key gene involved in endocytosis, increased MMP-2 activity in hypoxic HK-2 cells. It has been reported that activated Src (phospho-Src Tyr416) is a key molecule in multiple fibrotic pathways. However, whether Src functions on the regulation of Caveolin-1 and MMP-2 activity in hypoxic HK-2 cells remains poorly understood. To explore the underlying mechanism, a rat model of renal interstitial fibrosis was established, then we observed obvious hypoxia in fibrotic kidney tissue and the protein levels of phospho-Src and Caveolin-1 increased, while MMP-2 activity decreased. Next, we treated HK-2 cells with the phospho-Src inhibitor PP1. Compared with normal cells grown in hypoxia, in cells treated with PP1, the protein levels of phospho-Src and Caveolin-1 decreased, as did the protein levels of the MMP-2-activity-regulated molecules RECK (reversion-inducing-cysteine-rich protein with kazal motifs) and TIMP-2 (tissue inhibitor of metalloproteinase-2), while the protein level of MT1-MMP (membrane type 1-matrix metalloproteinase) increased and MMP-2 activity was enhanced. Therefore, hypoxia promotes the phosphorylation of Src and phospho-Src can enhance the endocytosis of HK-2 cells, which leads to decreased MMP-2 activity and aggravates renal interstitial fibrosis.
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