ArticleThe Journal of clinical investigation2015
Phosphatidylinositol 3-kinase signaling determines kidney size.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 65 citations in OpenAlex.
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- Therapeutic Effect of Lebanese Cannabis Oil Extract in the Management of Sodium Orthovanadate-Induced Nephrotoxicity in Rats.International journal of molecular sciences · 2025Article
- Pik3c3 expression profiling in the mouse kidney and its role in proximal tubule cell physiology.American journal of physiology. Cell physiology · 2024Article
- Lipidomic study of kidney in a mouse model with urine flow obstruction.Scientific reports · 2024Article
- Low potassium activation of proximal mTOR/AKT signaling is mediated by Kir4.2.Nature communications · 2024Article
- Age and Pre-operative HbA1c levels affect renal function compensation in living kidney donors.International urology and nephrology · 2024Review
- Metabolic Profiling of Rat Kidney Tissue Following Administration of D-Allulose.Journal of applied glycoscience · 2024Article
- Mechanisms of Diabetic Nephropathy Not Mediated by Hyperglycemia.Journal of clinical medicine · 2023Review
- Signaling mechanisms in renal compensatory hypertrophy revealed by multi-omics.Nature communications · 2023Article
- Accelerated cystogenesis by dietary protein load is dependent on, but not initiated by kidney macrophages.Frontiers in medicine · 2023Article
- Network Pharmacology and Experimental Validation to Explore That Celastrol Targeting PTEN is the Potential Mechanism ofDrug design, development and therapy · 2023Article
- Loss of Pten in Renal Tubular Cells Leads to Water Retention by Upregulating AQP2.Kidney diseases (Basel, Switzerland) · 2023Article
- Blocking ribosomal protein S6 phosphorylation inhibits podocyte hypertrophy and focal segmental glomerulosclerosis.Kidney international · 2022Article
- Divergent roles of angiotensin II upon the immediate and sustained increases of renal blood flow following unilateral nephrectomy.American journal of physiology. Renal physiology · 2022Article
- Article
- Myeloid PTEN deficiency aggravates renal inflammation and fibrosis in angiotensin II-induced hypertension.Journal of cellular physiology · 2022Article
- Review
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12 authors at 3 institutions in 1 country.
Funding
Abstract
Kidney size adaptively increases as mammals grow and in response to the loss of 1 kidney. It is not clear how kidneys size themselves or if the processes that adapt kidney mass to lean body mass also mediate renal hypertrophy following unilateral nephrectomy (UNX). Here, we demonstrated that mice harboring a proximal tubule-specific deletion of Pten (Pten(ptKO)) have greatly enlarged kidneys as the result of persistent activation of the class I PI3K/mTORC2/AKT pathway and an increase of the antiproliferative signals p21(Cip1/WAF) and p27(Kip1). Administration of rapamycin to Pten(ptKO) mice diminished hypertrophy. Proximal tubule-specific deletion of Egfr in Pten(ptKO) mice also attenuated class I PI3K/mTORC2/AKT signaling and reduced the size of enlarged kidneys. In Pten(ptKO) mice, UNX further increased mTORC1 activation and hypertrophy in the remaining kidney; however, mTORC2-dependent AKT phosphorylation did not increase further in the remaining kidney of Pten(ptKO) mice, nor was it induced in the remaining kidney of WT mice. After UNX, renal blood flow and amino acid delivery to the remaining kidney rose abruptly, followed by increased amino acid content and activation of a class III PI3K/mTORC1/S6K1 pathway. Thus, our findings demonstrate context-dependent roles for EGFR-modulated class I PI3K/mTORC2/AKT signaling in the normal adaptation of kidney size and PTEN-independent, nutrient-dependent class III PI3K/mTORC1/S6K1 signaling in the compensatory enlargement of the remaining kidney following UNX.
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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.