ArticleThe Journal of pathology2015
Loss of tumour suppressor PTEN expression in renal injury initiates SMAD3- and p53-dependent fibrotic responses.
Article in The Journal of pathology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
- Involvement of c-Myc/WWP1/TRIM65 Axis in Renal Fibrosis.Biomolecules · 2026Article
- The molecular mechanisms and therapeutic potential of p53 in kidney injury repair: a perspective on the p53alpha/delta133p53alpha signaling axis.Renal failure · 2025Review
- Hantaan virus glycoprotein Gc induces NEDD4-dependent PTEN ubiquitination and degradation to escape the restriction of autophagosomes and facilitate viral propagation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Aquaporin 1 is renoprotective in septic acute kidney injury by attenuating inflammation, apoptosis and fibrosis through inhibition of P53 expression.Frontiers in immunology · 2024Article
- PTEN in kidney diseases: a potential therapeutic target in preventing AKI-to-CKD transition.Frontiers in medicine · 2024Review
- Renoprotective Effect of Pitavastatin against TAA-Induced Renal Injury: Involvement of the miR-93/PTEN/AKT/mTOR Pathway.Advances in pharmacological and pharmaceutical sciences · 2024Article
- PAI-1 mediates TGF-β1-induced myofibroblast activation in tenocytes via mTOR signaling.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Article
- Loss of Pten in Renal Tubular Cells Leads to Water Retention by Upregulating AQP2.Kidney diseases (Basel, Switzerland) · 2023Article
- MicroRNA-10 Family Promotes the Epithelial-to-Mesenchymal Transition in Renal Fibrosis by the PTEN/Akt Pathway.Current issues in molecular biology · 2022Article
- Emerging role of tumor suppressor p53 in acute and chronic kidney diseases.Cellular and molecular life sciences : CMLS · 2022Review
- DNA methyltransferase 1 knockdown reverses PTEN and VDR by mediating demethylation of promoter and protects against renal injuries in hepatitis B virus-associated glomerulonephritis.Cell & bioscience · 2022Article
- Cancer-Associated Fibroblasts: Mechanisms of Tumor Progression and Novel Therapeutic Targets.Cancers · 2022Review
- PTEN alleviates maladaptive repair of renal tubular epithelial cells by restoring CHMP2A-mediated phagosome closure.Cell death & disease · 2021Article
- Article
- PTEN downregulation induces apoptosis and cell cycle arrest in uterine cervical cancer cells.Experimental and therapeutic medicine · 2021Article
- PAI-1 induction during kidney injury promotes fibrotic epithelial dysfunction via deregulation of klotho, p53, and TGF-β1-receptor signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- The Genomic Response to TGF-β1 Dictates Failed Repair and Progression of Fibrotic Disease in the Obstructed Kidney.Frontiers in cell and developmental biology · 2021Review
- PTEN Inhibition Accelerates Corneal Endothelial Wound Healing through Increased Endothelial Cell Division and Migration.Investigative ophthalmology & visual science · 2020Article
- Transcriptomic Analysis of Cellular Pathways in Healing Flexor Tendons of Plasminogen Activator Inhibitor 1 (PAI-1/Serpine1) Null Mice.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2020Article
- Blocking the histone lysine 79 methyltransferase DOT1L alleviates renal fibrosis through inhibition of renal fibroblast activation and epithelial-mesenchymal transition.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Deregulation of the tumour suppressor PTEN occurs in lung and skin fibrosis and diabetic and ischaemic renal injury. However, the potential role of PTEN and associated mechanisms in the progression of kidney fibrosis is unknown. Tubular and interstitial PTEN expression was dramatically decreased in several models of renal injury, including aristolochic acid nephropathy (AAN), streptozotocin (STZ)-mediated injury and ureteral unilateral obstruction (UUO), correlating with Akt, p53 and SMAD3 activation and fibrosis. Stable silencing of PTEN in HK-2 human tubular epithelial cells induced dedifferentiation and CTGF, PAI-1, vimentin, α-SMA and fibronectin expression, compared to HK-2 cells expressing control shRNA. Furthermore, PTEN knockdown stimulated Akt, SMAD3 and p53(Ser15) phosphorylation, with an accompanying decrease in population density and an increase in epithelial G1 cell cycle arrest. SMAD3 or p53 gene silencing or pharmacological blockade partially suppressed fibrotic gene expression and relieved growth inhibition orchestrated by deficiency or inhibition of PTEN. Similarly, shRNA suppression of PAI-1 rescued the PTEN loss-associated epithelial proliferative arrest. Moreover, TGFβ1-initiated fibrotic gene expression is further enhanced by PTEN depletion. Combined TGFβ1 treatment and PTEN silencing potentiated epithelial cell death via p53-dependent pathways. Thus, PTEN loss initiates tubular dysfunction via SMAD3- and p53-mediated fibrotic gene induction, with accompanying PAI-1-dependent proliferative arrest, and cooperates with TGFβ1 to induce the expression of profibrotic genes and tubular apoptosis.
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Registered trials
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