ArticleCell death and differentiation2019
Blockade of ALK4/5 signaling suppresses cadmium- and erastin-induced cell death in renal proximal tubular epithelial cells via distinct signaling mechanisms.
Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 81 citations in OpenAlex.
- Exploring the Association Between Potentially Toxic Elements and Chronic Kidney Disease of Unknown Etiology in Eastern Uttar Pradesh, India.Biological trace element research · 2026Article
- Targeting mitochondrial damage and ER stress to inhibit ferroptosis in cadmium-induced nephrotoxicity.Toxicology reports · 2025Review
- Ferroptosis: A key regulator and potential target for tissue injury.Histology and histopathology · 2025Review
- Downregulation of ferroptosis-related Genes can regulate the invasion and migration of osteosarcoma cells.Scientific reports · 2025Article
- IGF-Binding Protein 7 and Cadmium-Induced Hepatorenal Fibrosis.Journal of the American Society of Nephrology : JASN · 2025Article
- GPX4 expression changes in proximal tubule cells highlight the role of ferroptosis in IgAN.Scientific reports · 2025Article
- Iron-fueled ferroptosis: a new axis for immunomodulation to overcome cancer drug resistance-from immune microenvironment crosstalk to therapeutic translation.Frontiers in immunology · 2025Review
- The mutualistic relationship between M2c macrophages of TGFβ1 induction and gastric cancer cells: the correlation between protective mechanisms in the tumor microenvironment and polarization of subtypes of cells.Journal of Cancer · 2025Article
- [Research progress on metal pollutants inducing neurotoxicity through ferroptosis].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- A novel marine-derived anti-acute kidney injury agent targeting peroxiredoxin 1 and its nanodelivery strategy based on ADME optimization.Acta pharmaceutica Sinica. B · 2024Article
- Blockage of Akt activation suppresses cadmium-induced renal tubular cellular damages through aggrephagy in HK-2 cells.Scientific reports · 2024Article
- Article
- Qingxuan Runmu Yin alleviates dry eye disease via inhibition of the HMOX1/HIF-1 pathway affecting ferroptosis.Frontiers in pharmacology · 2024Article
- New insights into the ferroptosis and immune infiltration in endometriosis: a bioinformatics-based analysis.Frontiers in immunology · 2024Article
- Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases.Signal transduction and targeted therapy · 2023Review
- Insights into Endothelin Receptors in Pulmonary Hypertension.International journal of molecular sciences · 2023Review
- Study on the Correlation Between Regulatory Proteins of NBiological trace element research · 2023Article
- Understanding the mechanistic roles of environmental heavy metal stressors in regulating ferroptosis: adding new paradigms to the links with diseases.Apoptosis : an international journal on programmed cell death · 2023Review
- Chondroitin polymerizing factor predicts a poor prognosis and promotes breast cancer progression via the upstream TGF-β1/SMAD3 and JNK axis activation.Journal of cell communication and signaling · 2023Article
- Ferroptosis and mitochondrial dysfunction in acute central nervous system injury.Frontiers in cellular neuroscience · 2023Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Various types of cell death, including apoptosis, necrosis, necroptosis, and ferroptosis, are induced in renal tubular epithelial cells following exposure to environmental stresses and toxicants such as osmotic stress, ischemia/reperfusion injury, cisplatin, and cadmium. This is known to cause renal dysfunction, but the cellular events preceding stress-induced cell death in renal tubules are not fully elucidated. The activin receptor-like kinase (ALK) 4/5, also known as activin-transforming growth factor (TGF) β receptor, is involved in stress-induced renal injury. We, therefore, studied the role of ALK4/5 signaling in HK-2 human proximal tubular epithelial cell death induced by cisplatin, cadmium, hyperosmotic stress inducer, sorbitol, and the ferroptosis activator, erastin. We found that ALK4/5 signaling is involved in cadmium- and erastin-induced cell death, but not sorbitol- or cisplatin-induced apoptotic cell death. Cadmium exposure elevated the level of phosphorylated Smad3, and treatment with the ALK4/5 kinase inhibitors, SB431542 or SB505124, suppressed cadmium-induced HK-2 cell death. Cadmium-induced cell death was attenuated by siRNA-mediated ALK4 or Smad3 silencing, or by treatment with SIS3, a selective inhibitor of TGFβ1-dependent Smad3 phosphorylation. Furthermore, ALK4/5 signaling activated Akt signaling to promote cadmium-induced HK-2 cell death. In contrast, siRNA-mediated Inhibin-bA silencing or treatment with TGFβ1 or activin A had little effect on cadmium-induced HK-2 cell death. On the other hand, treatment with SB431542 or SB505124 attenuated erastin-induced ferroptosis by hyperactivating Nrf2 signaling in HK-2 cells. These results suggest that blockade of ALK4/5 signaling protects against cadmium- and erastin-induced HK-2 cell death via Akt and Nrf2 signaling pathways, respectively.
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