FASEB Journal

Our medical research library holds 8 studies published in FASEB Journal (1989–2025). Each entry links to the study's record on PubMed and, where there is one, to the publisher's page and a free full text. 8 have an abstract, the authors' own summary as PubMed records it: open "Abstract" to read it.

About the journal

• Publisher: Federation of American Societies for Experimental Biology
• Published: 1987 to the present, United States
• Language: English
• ISSN: 0892-6638 (print), 1530-6860 (electronic)
• Continues: Federation Proceedings
• Its record in the NLM Catalog

2020s

• Resveratrol Affects Cell Activities, Induces Apoptosis and Regulates AMPK Signaling Pathway in Pleural Mesothelioma Cells. M.R. Iaquinta, R. De Pace, A. Benkhalqui, et al. 2025;39(20):e71120. PubMed · Publisher · Free full text

  Abstract

  Pleural Mesothelioma (PM) is an aggressive tumor with a poor prognosis and limited therapeutic options. Despite the notion that resveratrol (RSV) significantly inhibits the growth of PM cancer cells, it is necessary to evaluate the effects of this stilbene as a tumor suppressor agent. In this work, the effects of the natural polyphenol were investigated on PM cell lines (MSTO-211H and IST-MES 2) to evaluate its action as a potential adjuvant agent, together with chemotherapy. Our results showed that RSV treatment was effective in PM cell lines, in particular in MSTO-211H. RES treatment decreases the viability evaluated with the MTT assay and Live/Dead staining. RSV stimulates the apoptotic process with positive staining for Annexin V-PI and Caspase-3/7 and inhibits the migration ability of both PM cell lines. In IST-MES 2, RSV causes a reduction in mitochondrial and cytoplasmic calcium levels. Moreover, RSV affects cellular morphology, E-cadherin protein expression, and decreased nuclear localization of β-catenin, attenuating Wnt/β-catenin signaling, which regulates tumor cell proliferation. At the molecular level, RSV modulated the expression of key genes that play an important role in cellular adhesion, proliferation, and metabolic activity, as well as AMPK signaling. RSV seems to be a promising therapeutic adjuvant agent for PM treatment.

  © 2025 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.

2010s

• Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells. P. Munson, Y.W. Lam, J. Dragon, et al. 2018;32(8):4328-4342. PubMed · Publisher · Free full text

  Abstract

  Asbestos exposure is a determinate cause of many diseases, such as mesothelioma, fibrosis, and lung cancer, and poses a major human health hazard. At this time, there are no identified biomarkers to demarcate asbestos exposure before the presentation of disease and symptoms, and there is only limited understanding of the underlying biology that governs asbestos-induced disease. In our study, we used exosomes, 30-140 nm extracellular vesicles, to gain insight into these knowledge gaps. As inhaled asbestos is first encountered by lung epithelial cells and macrophages, we hypothesize that asbestos-exposed cells secrete exosomes with signature proteomic cargo that can alter the gene expression of mesothelial cells, contributing to disease outcomes like mesothelioma. In the present study using lung epithelial cells (BEAS2B) and macrophages (THP-1), we first show that asbestos exposure causes changes in abundance of some proteins in the exosomes secreted from these cells. Furthermore, exposure of human mesothelial cells (HPM3) to these exosomes resulted in gene expression changes related to epithelial-to-mesenchymal transition and other cancer-related genes. This is the first report to indicate that asbestos-exposed cells secrete exosomes with differentially abundant proteins and that those exosomes have a gene-altering effect on mesothelial cells.-Munson, P., Lam, Y.-W., Dragon, J. MacPherson, M., Shukla, A. Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells.

• Macrophages utilize the mitochondrial calcium uniporter for profibrotic polarization. L. Gu, J.L. Larson-Casey, A.B. Carter. 2017;31(7):3072-3083. PubMed · Publisher · Free full text

  Abstract

  Fibrosis in multiple organs, including the liver, kidney, and lung, often occurs secondary to environmental exposure. Asbestos exposure is one important environmental cause of lung fibrosis. The mechanisms that mediate fibrosis is not fully understood, although mitochondrial oxidative stress in alveolar macrophages is critical for fibrosis development. Mitochondrial Ca2+ levels can be associated with production of reactive oxygen species. Here, we show that patients with asbestosis have higher levels of mitochondrial Ca2+ compared with normal patients. The mitochondrial calcium uniporter (MCU) is a highly selective ion channel that transports Ca2+ into the mitochondrial matrix to modulate metabolism. Asbestos exposure increased mitochondrial Ca2+ influx in alveolar macrophages from wild-type, but not MCU+/-, mice. MCU expression polarized macrophages to a profibrotic phenotype after exposure to asbestos, and the profibrotic polarization was regulated by MCU-mediated ATP production. Profibrotic polarization was abrogated when MCU was absent or its activity was blocked. Of more importance, mice that were deficient in MCU were protected from pulmonary fibrosis. Regulation of mitochondrial Ca2+ suggests that MCU may play a pivotal role in the development of fibrosis and could potentially be a therapeutic target for pulmonary fibrosis.-Gu, L., Larson-Casey, J. L., Carter, A. B. Macrophages utilize the mitochondrial calcium uniporter for profibrotic polarization.

  © FASEB.

• SIRT3 deficiency promotes lung fibrosis by augmenting alveolar epithelial cell mitochondrial DNA damage and apoptosis. R.P. Jablonski, S.J. Kim, P. Cheresh, et al. 2017;31(6):2520-2532. PubMed · Publisher · Free full text

  Abstract

  Alveolar epithelial cell (AEC) mitochondrial dysfunction and apoptosis are important in idiopathic pulmonary fibrosis and asbestosis. Sirtuin 3 (SIRT3) detoxifies mitochondrial reactive oxygen species, in part, by deacetylating manganese superoxide dismutase (MnSOD) and mitochondrial 8-oxoguanine DNA glycosylase. We reasoned that SIRT3 deficiency occurs in fibrotic lungs and thereby augments AEC mtDNA damage and apoptosis. Human lungs were assessed by using immunohistochemistry for SIRT3 activity via acetylated MnSODK68 Murine AEC SIRT3 and cleaved caspase-9 (CC-9) expression were assayed by immunoblotting with or without SIRT3 enforced expression or silencing. mtDNA damage was measured by using quantitative PCR and apoptosis via ELISA. Pulmonary fibrosis after asbestos or bleomycin exposure was evaluated in 129SJ/wild-type and SIRT3-knockout mice (Sirt3-/- ) by using fibrosis scoring and lung collagen levels. Idiopathic pulmonary fibrosis lung alveolar type II cells have increased MnSODK68 acetylation compared with controls. Asbestos and H2O2 diminished AEC SIRT3 protein expression and increased mitochondrial protein acetylation, including MnSODK68 SIRT3 enforced expression reduced oxidant-induced AEC OGG1K338/341 acetylation, mtDNA damage, and apoptosis, whereas SIRT3 silencing promoted these effects. Asbestos- or bleomycin-induced lung fibrosis, AEC mtDNA damage, and apoptosis in wild-type mice were amplified in Sirt3-/- animals. These data suggest a novel role for SIRT3 deficiency in mediating AEC mtDNA damage, apoptosis, and lung fibrosis.-Jablonski, R. P., Kim, S.-J., Cheresh, P., Williams, D. B., Morales-Nebreda, L., Cheng, Y., Yeldandi, A., Bhorade, S., Pardo, A., Selman, M., Ridge, K., Gius, D., Budinger, G. R. S., Kamp, D. W. SIRT3 deficiency promotes lung fibrosis by augmenting alveolar epithelial cell mitochondrial DNA damage and apoptosis.

  © FASEB.

• Alternative activation of macrophages and pulmonary fibrosis are modulated by scavenger receptor, macrophage receptor with collagenous structure. S. Murthy, J.L. Larson-Casey, A.J. Ryan, et al. 2015;29(8):3527-36. PubMed · Publisher · Free full text

  Abstract

  Alternative activation of alveolar macrophages is linked to fibrosis following exposure to asbestos. The scavenger receptor, macrophage receptor with collagenous structure (MARCO), provides innate immune defense against inhaled particles and pathogens; however, a receptor for asbestos has not been identified. We hypothesized that MARCO acts as an initial signaling receptor for asbestos, polarizes macrophages to a profibrotic M2 phenotype, and is required for the development of asbestos-induced fibrosis. Compared with normal subjects, alveolar macrophages isolated from patients with asbestosis express higher amounts of MARCO and have greater profibrotic polarization. Arginase 1 (40-fold) and IL-10 (265-fold) were higher in patients. In vivo, the genetic deletion of MARCO attenuated the profibrotic environment and pulmonary fibrosis in mice exposed to chrysotile. Moreover, alveolar macrophages from MARCO(-/-) mice polarize to an M1 phenotype, whereas wild-type mice have higher Ym1 (>3.0-fold) and nearly 7-fold more active TGF-β1 in bronchoalveolar lavage (BAL) fluid (BALF). Arg(432) and Arg(434) in domain V of MARCO are required for the polarization of macrophages to a profibrotic phenotype as mutation of these residues reduced FIZZ1 expression (17-fold) compared with cells expressing MARCO. These observations demonstrate that a macrophage membrane protein regulates the fibrotic response to lung injury and suggest a novel target for therapeutic intervention.

  © FASEB.

2000s

• Transcriptional up-regulation of MMP12 and MMP13 by asbestos occurs via a PKCdelta-dependent pathway in murine lung. A. Shukla, T.F. Barrett, K.I. Nakayama, et al. 2006;20(7):997-9. PubMed · Publisher

  Abstract

  Asbestos is a known inflammatory, carcinogenic, and fibrotic agent, but the mechanisms leading to asbestos-induced lung diseases are unclear. Using a murine inhalation model of fibrogenesis, we show that asbestos causes significant increases in mRNA levels of lung matrix metalloproteinases (MMPs 12 and 13) and tissue inhibitor of metalloproteinases (TIMP1), as well as increased activities of MMP 2, 9, and 12 in bronchoalveolar lavage fluids (BALF). Asbestos-exposed PKCdelta knockout (PKCdelta-/-) mice exhibited decreased expression of lung MMP12 and MMP13 compared with asbestos-exposed wild-type mice. Studies using small molecule inhibitors in murine alveolar epithelial type II cells (C10) and primary lung fibroblasts confirmed that asbestos transcriptionally up-regulates MMPs via an EGFR (or other growth factor receptors)/PI3K/PKCdelta/ERK1/2 pathway. Moreover, use of a broad-spectrum MMP inhibitor showed that MMPs play an important role in further enhancing asbestos-induced signaling events by activating EGFR. These data reveal a potentially important link between asbestos signaling and integrity of the extracellular matrix (ECM) that likely contributes to asbestos-induced lung remodeling and diseases.

1990s

• Active oxygen species mediate asbestos fiber uptake by tracheal epithelial cells. J. Hobson, J.L. Wright, A. Churg. 1990;4(13):3135-9. PubMed · Publisher

  Abstract

  To examine the mechanism whereby asbestos fibers penetrate tracheal epithelial cells, we exposed rat tracheal explants to amosite asbestos alone, or with varying concentrations of substances that scavenge active oxygen species (catalase and superoxide dismutase) or prevent formation of active oxygen species (deferoxamine). All three agents decreased asbestos fiber uptake in a dose-response fashion, but no agent provided complete protection against fiber penetration. We conclude that uptake of amosite asbestos fibers is mediated in part by active oxygen species (most likely OH.), but that other mechanisms of fiber uptake must also exist.

1980s

• Induction of angiogenesis by intraperitoneal injection of asbestos fibers. R.M. Branchaud, J.L. MacDonald, A.B. Kane. 1989;3(6):1747-52. PubMed · Publisher

  Abstract

  Tumors and activated macrophages release angiogenic factors that stimulate migration and proliferation of capillaries. We studied the development of angiogenesis before the appearance of mesotheliomas in C57B1/6 mice. Weekly i.p. injections of crocidolite asbestos fibers produced mesotheliomas after 30-50 wk. The initial histologic response to asbestos fibers was a nodular lesion on the peritoneal lining composed of clusters of fibers, activated macrophages, and proliferating mesenchymal cells. The earliest visible evidence of angiogenesis was seen surrounding 7% of these lesions 14 days after a single injection of 200 micrograms of crocidolite asbestos fibers. After six weekly injections, 30% of the lesions containing asbestos fibers were surrounded by a capillary network radiating toward the center of the lesion. Other mineral fibers, including chrysotile asbestos and fiberglass, also induced angiogenesis after six weekly injections. In contrast, only 8% of the lesions containing short asbestos fibers (90.6% less than or equal to 2.0 microns) and 9% of the lesions containing silica particles showed evidence of angiogenesis. We conclude that tumorigenic mineral fibers induce angiogenesis in the peritoneal lining, whereas nontumorigenic mineral particles or short asbestos fibers are less effective. Ingrowth of new blood vessels around clusters of asbestos fibers may facilitate the later emergence of mesotheliomas at these sites.

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