ArticleAutophagy2014
Autophagy fosters myofibroblast differentiation through MTORC2 activation and downstream upregulation of CTGF.
Article in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 2 syntheses or guidelines pooled it, 84 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Rewiring autophagy to target cutaneous wound healing: investigation of molecular mechanisms to therapeutic interventions.Molecular biology reports · 2026Review
- Dual Roles of Autophagy in Endometrial Fibrosis and Its Implications in Age-Related Reproductive Dysfunction.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Matrix stiffness induced CREB3L1 activation contributed to skin fibrosis through calcium influx triggered endoplasmic reticulum stress.Cellular and molecular life sciences : CMLS · 2026Article
- DDIT3 Promotes Starvation-Induced Autophagy via ER Stress in Vero Cells.International journal of molecular sciences · 2026Article
- Autophagy in the liver.Autophagy reports · 2026Review
- Leptin-dependent fat accumulation triggers autophagy in metabolic dysfunction-associated steatohepatitis model.Translational gastroenterology and hepatology · 2026Article
- Pathological Interplay of ROS With Myofibroblasts: An Impediment to Corneal Restitution.Oxidative medicine and cellular longevity · 2026Review
- Article
- Fibroblast-Myofibroblast Transition in Osteoarthritis Progression: Current Insights.International journal of molecular sciences · 2025Review
- Autophagy in orthodontic tooth movement: advances, challenges, and future perspectives.Molecular medicine (Cambridge, Mass.) · 2025Review
- Autophagy in Tissue Repair and Regeneration.Cells · 2025Review
- Autophagy in the lung: guardian of homeostasis or driver of disease.Autophagy reports · 2025Review
- MiR-155-5p regulates autophagy and apoptosis of glioma cells through RICTOR.Translational cancer research · 2024Article
- Pathogenesis and management of renal fibrosis induced by unilateral ureteral obstruction.Kidney research and clinical practice · 2024Article
- The cellular adaptor GULP1 interacts with ATG14 to potentiate autophagy and APP processing.Cellular and molecular life sciences : CMLS · 2024Article
- BAG3 localizes to mitochondria in cardiac fibroblasts and regulates mitophagy.American journal of physiology. Heart and circulatory physiology · 2024Article
- Glutaminolysis regulates endometrial fibrosis in intrauterine adhesion via modulating mitochondrial function.Biological research · 2024Article
- PDGF-BB accelerates TSCC via fibroblast lactates limiting miR-26a-5p and boosting mitophagy.Cancer cell international · 2024Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Recent evidence suggests that autophagy may favor fibrosis through enhanced differentiation of fibroblasts in myofibroblasts. Here, we sought to characterize the mediators and signaling pathways implicated in autophagy-induced myofibroblast differentiation. Fibroblasts, serum starved for up to 4 d, showed increased LC3-II/-I ratios and decreased SQSTM1/p62 levels. Autophagy was associated with acquisition of markers of myofibroblast differentiation including increased protein levels of ACTA2/αSMA (actin, α 2, smooth muscle, aorta), enhanced gene and protein levels of COL1A1 (collagen, type I, α 1) and COL3A1, and the formation of stress fibers. Inhibiting autophagy with 3 different class I phosphoinositide 3-kinase and class III phosphatidylinositol 3-kinase (PtdIns3K) inhibitors or through ATG7 silencing prevented myofibroblast differentiation. Autophagic fibroblasts showed increased expression and secretion of CTGF (connective tissue growth factor), and CTGF silencing prevented myofibroblast differentiation. Phosphorylation of the MTORC1 target RPS6KB1/p70S6K kinase was abolished in starved fibroblasts. Phosphorylation of AKT at Ser473, a MTORC2 target, was reduced after initiation of starvation but was followed by spontaneous rephosphorylation after 2 d of starvation, suggesting the reactivation of MTORC2 with sustained autophagy. Inhibiting MTORC2 activation with long-term exposure to rapamycin or by silencing RICTOR, a central component of the MTORC2 complex abolished AKT rephosphorylation. Both RICTOR silencing and rapamycin treatment prevented CTGF and ACTA2 upregulation, demonstrating the central role of MTORC2 activation in CTGF induction and myofibroblast differentiation. Finally, inhibition of autophagy with PtdIns3K inhibitors or ATG7 silencing blocked AKT rephosphorylation. Collectively, these results identify autophagy as a novel activator of MTORC2 signaling leading to CTGF induction and myofibroblast differentiation.
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What OpenQuestion holds
Registered trials
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.