ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Ionizing radiation induces myofibroblast differentiation via lactate dehydrogenase.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
36 citing papers in PubMed, 46 citations in OpenAlex.
- pH responsive nanoplatforms for radiosensitization and radioprotection in cancer therapy.Discover oncology · 2026Review
- First Insights on the Upcoming Role of Next-Generation PLLA-LASYNPRO in Aesthetic and Regenerative Medicine: A Survey of Experts-the PLLA-LASYNPRO Rationale.Facial plastic surgery : FPS · 2026Article
- The pentose phosphate pathway contributes to excess lactate production in radiation-induced fibroblast to myofibroblast transdifferentiation.The Journal of biological chemistry · 2026Article
- Review
- Cancer-associated fibroblasts as architects of acquired immune-privileged-like niches in gastrointestinal cancers: lessons from ocular immune privilege and barrier biology.Frontiers in immunology · 2026Review
- Review
- Lactate-mediated lactylation in human health and diseases: Progress and remaining challenges.Journal of advanced research · 2025Review
- Inhibition of GPR68 induces ferroptosis and radiosensitivity in diverse cancer cell types.Scientific reports · 2025Article
- Tissue fibrosis induced by radiotherapy: current understanding of the molecular mechanisms, diagnosis and therapeutic advances.Journal of translational medicine · 2023Review
- Exhaled breath condensate identifies metabolic dysregulation in patients with radiation-induced lung injury.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Natural compounds as lactate dehydrogenase inhibitors: potential therapeutics for lactate dehydrogenase inhibitors-related diseases.Frontiers in pharmacology · 2023Review
- Tolerogenic dendritic cells in radiation-induced lung injury.Frontiers in immunology · 2023Review
- Monophosphoryl lipid A ameliorates radiation-induced lung injury by promoting the polarization of macrophages to the M1 phenotype.Journal of translational medicine · 2022Article
- The Novel Small Molecule BTB Inhibits Pro-Fibrotic Fibroblast Behavior though Inhibition of RhoA Activity.International journal of molecular sciences · 2022Article
- miR-338-3p blocks TGFβ-induced myofibroblast differentiation through the induction of PTEN.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- All for one, though not one for all: team players in normal tissue radiobiology.International journal of radiation biology · 2022Review
- Effect of PD-1 Inhibitor Combined with X-Ray Irradiation on the Inflammatory Microenvironment and Lung Tissue Injury in Mice.Journal of inflammation research · 2022Article
- Glycolytic Reprogramming in Silica-Induced Lung Macrophages and Silicosis Reversed by Ac-SDKP Treatment.International journal of molecular sciences · 2021Article
- The NaCellular and molecular life sciences : CMLS · 2021Review
- Mechanobiological Implications of Cancer Progression in Space.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Pulmonary fibrosis is a common and dose-limiting side-effect of ionizing radiation used to treat cancers of the thoracic region. Few effective therapies are available for this disease. Pulmonary fibrosis is characterized by an accumulation of myofibroblasts and excess deposition of extracellular matrix proteins. Although prior studies have reported that ionizing radiation induces fibroblast to myofibroblast differentiation and collagen production, the mechanism remains unclear. Transforming growth factor-β (TGF-β) is a key profibrotic cytokine that drives myofibroblast differentiation and extracellular matrix production. However, its activation and precise role in radiation-induced fibrosis are poorly understood. Recently, we reported that lactate activates latent TGF-β through a pH-dependent mechanism. Here, we wanted to test the hypothesis that ionizing radiation leads to excessive lactate production via expression of the enzyme lactate dehydrogenase-A (LDHA) to promote myofibroblast differentiation. We found that LDHA expression is increased in human and animal lung tissue exposed to ionizing radiation. We demonstrate that ionizing radiation induces LDHA, lactate production, and extracellular acidification in primary human lung fibroblasts in a dose-dependent manner. We also demonstrate that genetic and pharmacologic inhibition of LDHA protects against radiation-induced myofibroblast differentiation. Furthermore, LDHA inhibition protects from radiation-induced activation of TGF-β. We propose a profibrotic feed forward loop, in which radiation induces LDHA expression and lactate production, which can lead to further activation of TGF-β to drive the fibrotic process. These studies support the concept of LDHA as an important therapeutic target in radiation-induced pulmonary fibrosis.
Indexed as
Identifiers
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.