المؤلفون: Eri Mori, Teppei Takeda, Jun Araya, Tsukasa Kadota, Shun Inukai, Daisuke Takekoshi, Satoki Hatano, Kazuhiro Omura, Shota Fujimoto, Kazuyoshi Kuwano

المصدر: Internal Medicine. 61:1877-1880

مصطلحات موضوعية: medicine.medical_specialty, rhinorrhea, Lung, Cerebrospinal Fluid Leak, Cerebrospinal Fluid Rhinorrhea, business.industry, Pneumonia, General Medicine, respiratory system, Aspiration pneumonia, medicine.disease, respiratory tract diseases, Surgery, medicine.anatomical_structure, Cerebrospinal fluid, Internal Medicine, Humans, Medicine, Meningitis, medicine.symptom, business, Complication

الوصف: We herein report two cases of cerebrospinal fluid (CSF) rhinorrhea associated with lung infiltrates. One patient presented with symptomatic non-resolving pneumonia, while the other was asymptomatic. In both cases, the lung infiltrates completely resolved when CSF leakage had subsided. Pulmonary involvement in CSF rhinorrhea is under-recognized, and despite being the definitive treatment, surgery for CSF rhinorrhea is typically postponed due to the presence of lung infiltrates. However, meningitis is a serious complication due to a delay in surgical management. Physicians should be made aware that CSF rhinorrhea is a potential cause of intractable lung infiltrates.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3f8b08e962f24710261946a60ce79b78Test
https://doi.org/10.2169/internalmedicine.8596-21Test

المؤلفون: Kazuyoshi Kuwano, Daisuke Takekoshi, Hirohumi Utsumi, Yoshinori Kawabata, Hiromichi Hara, Mitsuo Hashimoto, Jun Araya, Rei Makishima, Hiroshi Wakui, Masahiro Ikegami, Hanae Miyagawa, Takuya Akutsu, Junko Watanabe, Ayako Nishioka, Yuma Matsui, Yuki Noda, Takanori Numata, Shunsuke Minagawa, Ayu Kiritani, Keitaro Okuda

المصدر: Internal Medicine

مصطلحات موضوعية: Male, medicine.medical_specialty, Non-specific interstitial pneumonia, Corticosteroid treatment, Dasatinib, Case Report, Lung biopsy, 030204 cardiovascular system & hematology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, chronic myeloid leukemia, Internal medicine, hemic and lymphatic diseases, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Internal Medicine, medicine, non-specific interstitial pneumonia, Humans, Interstitial pneumonia, Lung, Protein Kinase Inhibitors, interstitial lung disease, business.industry, Interstitial lung disease, Myeloid leukemia, General Medicine, respiratory system, Middle Aged, medicine.disease, respiratory tract diseases, 030211 gastroenterology & hepatology, business, Lung Diseases, Interstitial, Bosutinib, medicine.drug

الوصف: We report the case of a 56-year-old man with chronic myeloid leukemia (CML) who developed dasatinib-induced interstitial lung disease (ILD) 7 years after starting dasatinib, a BCR-ABL1 inhibitor. The patient presented with dyspnea. Chest imaging showed diffuse ground-glass opacities. A surgical lung biopsy showed cellular non-specific interstitial pneumonia (NSIP). Corticosteroid treatment ameliorated his condition. Bosutinib, another BCR-ABL1 inhibitor, was successfully re-instituted. The present case and relevant literature suggest that dasatinib-induced ILD can present as NSIP after an extended period, responds to corticosteroids, and is amenable to re-challenge at a lower-dose or with alternative BCR-ABL1 inhibitors.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::30f5a755d5bc85c338129fed0eb3db1cTest
http://europepmc.org/articles/PMC7578610Test

المؤلفون: Hiromochi Hara, Mitsuo Hashimoto, Hironori Kawamoto, Nayuta Saito, Jun Araya, Shunsuke Minagawa, Tsukasa Kadota, Yu Fujita, Saburo Ito, Akihiko Ito, Akihiro Ichikawa, Daisuke Takekoshi, Naoaki Watanabe, Kazuyoshi Kuwano, Yusuke Hosaka, Shota Fujimoto

المصدر: 03.02 - Airway cell biology and immunopathology.

مصطلحات موضوعية: COPD, Lung, business.industry, Autophagy, medicine.disease, respiratory tract diseases, Cell biology, Lipofuscin, Pathogenesis, stomatognathic diseases, medicine.anatomical_structure, Aggresome, Lysosome, otorhinolaryngologic diseases, medicine, business, Function (biology)

الوصف: Introduction: Insufficient autophagic degradation has been implicated in accelerated cellular senescence during chronic obstructive pulmonary disease (COPD) pathogenesis. Cigarette smoke (CS)-induced functional deterioration of lysosomes may be associated with impaired autophagy. Lysosomal membrane permeabilization (LMP) is indicative of damaged lysosomes, and galectin-3 and tripartite motif proteins (TRIM)16 play a cooperative role in recognizing LMP and inducing lysophagy, a lysosome selective autophagy for maintaining lysosome function. Methods: To examine the role of TRIM16-mediated lysophagy in regulating CS-induced LMP and cellular senescence during COPD pathogenesis, using human bronchial epithelial cells (HBEC) and lung tissues. Results: CS extract (CSE) induced LMP as detected by galectin-3 accumulation and TRIM16 was involved in CSE-induced lysophagy. Impaired lysophagy was associated with lysosomal dysfunction and accelerated cellular senescence. Airway epithelial cells in COPD lungs showed increase in lipofuscin, aggresome, and galectin-3 puncta reflecting accumulation of lysosomal damage with concomitantly reduced TRIM16 expression levels. HBEC isolated from COPD patients showed reduced TRIM16 but increased galectin-3, and a negative correlation between TRIM16 and galectin-3 protein levels was demonstrated. Conclusion: Damaged lysosomes with LMP are accumulated in epithelial cells in COPD lungs, which can be at least partly attributed to impaired TRIM16-mediated lysophagy. Increased LMP in lung epithelial cells may be responsible for COPD pathogenesis through the enhancement of cellular senescence.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::1e1c1e0d5645c1d962573577d6ac9409Test
https://doi.org/10.1183/23120541.lsc-2021.69Test

المؤلفون: Tsukasa Kadota, Jun Araya, Yu Fujita, Naoaki Watanabe, Kazuyoshi Kuwano, J Nakayama, Yusuke Yamamoto

المصدر: 03.01 - Molecular pathology and funct. genomics.

مصطلحات موضوعية: Chemokine, Stromal cell, biology, business.industry, Cellular differentiation, Cell, Phenotype, Deep sequencing, respiratory tract diseases, Cell biology, CXCL1, medicine.anatomical_structure, Immune system, biology.protein, Medicine, business

الوصف: The development of high-throughput single-cell RNA sequencing (scRNA-seq) has provided a new research tool to obtain gene expression profiles at single-cell resolution and identify novel cellular phenotypes in lung diseases. To elucidate the cell-specific mechanisms contributing to COPD pathogenesis, we used scRNA-seq to dissect cellular and molecular features of COPD and elucidate differences in the proportions and transcriptional phenotypes of epithelial cells between COPD patients, non-COPD smokers, and never-smokers. We sequenced 57,755 cells and achieved, on average, a sequencing depth of 112,482 reads per cell and 1,693 genes per cell. While epithelial components in never-smokers were relatively uniform, the smoker groups presented with extensive heterogeneity in epithelial cells, particularly in the alveolar type 2 (AT2) lineages. Notably, we identified a novel subpopulation of AT2 epithelial cells that emerged in COPD patients, and specifically expressed PD-L1 and a number of chemokines such as CXCL1 and CCL2. A trajectory analysis revealed that the inflammatory AT2 cell subpopulation followed a unique differentiation path, and a prediction model of cell-to-cell interactions inferred increased intercellular networks of inflammatory AT2 cells with immune and stromal cell populations. Our analysis reveals a unique cellular differentiation pathway and function underlying the biological and clinical characteristics of COPD pathogenesis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::6f219a2bbb2bff61c410fb9344818394Test
https://doi.org/10.1183/23120541.lsc-2021.36Test

المؤلفون: Tsukasa Kadota, Kenji Kobayashi, Yusuke Kurita, Saburo Ito, Katsutoshi Nakayama, Hiromichi Hara, Makoto Odaka, Takanori Numata, Hiroshi Wakui, Yumi Kaneko, Kazuya Tsubouchi, Shohei Mori, Akihiro Ichikawa, Makoto Yamashita, Yusuke Hosaka, Shunsuke Minagawa, Hirotaka Imai, Hisatoshi Asano, Kazuyoshi Kuwano, Nayuta Saito, Nahoko Sato, Masahiro Yoshida, Toshiaki Morikawa, Taro Sakamoto, Hirohumi Utsumi, Jun Araya, Takeo Iwamoto

المصدر: Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019)
Nature Communications

مصطلحات موضوعية: 0301 basic medicine, General Physics and Astronomy, 02 engineering and technology, GPX4, medicine.disease_cause, Pathogenesis, Lipid peroxidation, chemistry.chemical_compound, Pulmonary Disease, Chronic Obstructive, lcsh:Science, Phospholipids, COPD, Multidisciplinary, biology, Chronic obstructive pulmonary disease, Smoking, respiratory system, 021001 nanoscience & nanotechnology, Deferoxamine, 0210 nano-technology, medicine.drug, Cell death, Programmed cell death, Iron, Science, Nuclear Receptor Coactivators, Mice, Transgenic, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, medicine, Animals, Ferroptosis, Humans, business.industry, Epithelial Cells, General Chemistry, medicine.disease, respiratory tract diseases, Ferritin, Mice, Inbred C57BL, 030104 developmental biology, chemistry, biology.protein, Cancer research, lcsh:Q, Lipid Peroxidation, business, Reactive Oxygen Species, Oxidative stress

الوصف: Ferroptosis is a necrotic form of regulated cell death (RCD) mediated by phospholipid peroxidation in association with free iron-mediated Fenton reactions. Disrupted iron homeostasis resulting in excessive oxidative stress has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, we demonstrate the involvement of ferroptosis in COPD pathogenesis. Our in vivo and in vitro models show labile iron accumulation and enhanced lipid peroxidation with concomitant non-apoptotic cell death during cigarette smoke (CS) exposure, which are negatively regulated by GPx4 activity. Treatment with deferoxamine and ferrostatin-1, in addition to GPx4 knockdown, illuminate the role of ferroptosis in CS-treated lung epithelial cells. NCOA4-mediated ferritin selective autophagy (ferritinophagy) is initiated during ferritin degradation in response to CS treatment. CS exposure models, using both GPx4-deficient and overexpressing mice, clarify the pivotal role of GPx4-regulated cell death during COPD. These findings support a role for cigarette smoke-induced ferroptosis in the pathogenesis of COPD.
Altered iron homeostasis resulting in excessive oxidative stress has been implicated in smoke-induced lung diseases. Here the authors show that ferroptosis of lung epithelial cells, potentially resulting from excessive ferritinophagy, is involved in the pathogenesis of COPD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::841b34bc8bc50cc9523737c8cc820ffeTest
https://doaj.org/article/7f973dabdbee4e05bfa82fda5c334da7Test

المؤلفون: Mi So Kim, Ae-Rin Baek, Ji Min Lee, Do Jin Kim, Shunsuke Minagawa, Masahiro Yoshida, Su Sie Chin, An Soo Jang, Choon-Sik Park, Sung Woo Park, June-Hyuk Lee, Jun Araya, Kazuyoshi Kuwano

المصدر: American Journal of Respiratory Cell and Molecular Biology. 59:215-224

مصطلحات موضوعية: 0301 basic medicine, Pulmonary and Respiratory Medicine, Programmed cell death, Necroptosis, Clinical Biochemistry, Apoptosis, Kidney, Bleomycin, Pathogenesis, Mice, Necrosis, 03 medical and health sciences, chemistry.chemical_compound, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Fibrosis, medicine, Animals, Humans, Molecular Biology, Lung, Caspase 3, business.industry, Graft Survival, Epithelial Cells, Cell Biology, respiratory system, medicine.disease, respiratory tract diseases, 030104 developmental biology, medicine.anatomical_structure, chemistry, Receptor-Interacting Protein Serine-Threonine Kinases, 030220 oncology & carcinogenesis, Cancer research, business

الوصف: Alveolar epithelial cell (AEC) injury leading to cell death is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF). Among regulated/programmed cell death, the excessive apoptosis of AECs has been widely implicated in IPF pathogenesis. Necroptosis is a type of regulated/programmed necrosis. A multiprotein complex composed of receptor-interacting protein kinase (RIPK)-1 and -3 plays a key regulatory role in initiating necroptosis. Although necroptosis participates in disease pathogeneses through the release of damage-associated molecular patterns, its association with IPF progression remains elusive. In this study, we attempted to illuminate the involvement of RIPK3-regulated necroptosis in IPF pathogenesis. IPF lung tissues were used to detect necroptosis, and the role of RIPK3 was determined using cell culturing models of AECs. Lung fibrosis models of bleomycin (BLM) treatment were also used. RIPK3 expression levels were increased in IPF lungs, and both apoptosis and necroptosis were detected mainly in AECs. Necrostatin-1 and RIPK3 knockout experiments in AECs revealed the participation of necroptosis in BLM and hydrogen peroxide-induced cell death. BLM treatment induced RIPK3 expression in AECs and increased high-mobility group box 1 and IL-1β levels in mouse lungs. The efficient attenuation of BLM-induced lung inflammation and fibrosis was determined in RIPK3 knockout mice and by necrostatin-1 with a concomitant reduction in high-mobility group box 1 and IL-1β. RIPK3-regulated necroptosis in AECs is involved in the mechanism of lung fibrosis development through the release of damage-associated molecular patterns as part of the pathogenic sequence of IPF.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::628e6e52d56d96daf1247c27d3c1a5e9Test
https://doi.org/10.1165/rcmb.2017-0034ocTest

المؤلفون: Iwao Shimomura, Takashi Ohtsuka, Tsukasa Kadota, Jun Nakayama, Yu Fujita, Jun Araya, Yutaro Mori, Koji Okamoto, Yusuke Yamamoto, Naoaki Watanabe, Kazuyoshi Kuwano

مصطلحات موضوعية: COPD, Chemokine, Stromal cell, biology, business.industry, Cellular differentiation, Cell, medicine.disease, respiratory tract diseases, Pathogenesis, Transcriptome, Immune system, medicine.anatomical_structure, Immunology, biology.protein, Medicine, business

الوصف: Phenotypic alterations in the lung epithelium have been widely implicated in Chronic obstructive pulmonary disease (COPD) pathogenesis, but the precise mechanisms orchestrating this persistent inflammatory process remain unknown due to the complexity of lung parenchymal and mesenchymal architecture. To identify cell type-specific mechanisms and cell-cell interactions among the multiple lung resident cell types and inflammatory cells that contribute to COPD progression, we profiled 52,764 cells from lungs of COPD patients, non-COPD smokers, and never smokers using single-cell RNA sequencing technology. We predicted pseudotime of cell differentiation and cell-to-cell interaction networks in COPD. While epithelial components in never-smokers were relatively uniform, smoker groups represent extensive heterogeneity in epithelial cells, particularly in alveolar type 2 (AT2) clusters. Among AT2 cells, which are generally regarded as alveolar progenitors, we identified a unique subset that significantly increased in COPD patients, and specifically expressed a series of chemokines and PD-L1. A trajectory analysis revealed that the inflammatory AT2 cell subpopulation followed a unique differentiation path, and a prediction model of cell-to-cell interactions inferred significantly increased intercellular networks of inflammatory AT2 cells. Our results identify previously unidentified cell subsets and provide an insight into the biological and clinical characteristics of COPD pathogenesis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::2f0f660f2e2d2d53321fce5c7c1249d4Test
https://doi.org/10.1101/2020.12.03.20242412Test

المؤلفون: Takanori Numata, Yusuke Hosaka, Nayuta Saito, Shota Fujimoto, Akihiro Ichikawa, Jun Hirano, Saburo Ito, Daisuke Takekoshi, Tsukasa Kadota, Katsutoshi Nakayama, Jun Araya, Keitaro Okuda, Hideki Matsudaira, Hirofumi Utsumi, Takashi Ohtsuka, Shunsuke Minagawa, Yu Fujita, Mitsuo Hashimoto, Hiromichi Hara, Junko Watanabe, Hironori Kawamoto, Hiroshi Wakui, Masahiro Yoshida, Shohei Mori, Kazuyoshi Kuwano, Akihiko Ito, Naoaki Watanabe, Hanae Miyagawa

المصدر: Journal of immunology (Baltimore, Md. : 1950). 207(1)

مصطلحات موضوعية: Ubiquitin-Protein Ligases, Immunology, Lipofuscin, Pathogenesis, Tripartite Motif Proteins, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Lysosome, otorhinolaryngologic diseases, medicine, Immunology and Allergy, Humans, Cells, Cultured, COPD, Lung, business.industry, Autophagy, Hydrogen-Ion Concentration, medicine.disease, respiratory tract diseases, stomatognathic diseases, medicine.anatomical_structure, Aggresome, Cancer research, business, Lysosomes, Function (biology), 030215 immunology

الوصف: Insufficient autophagic degradation has been implicated in accelerated cellular senescence during chronic obstructive pulmonary disease (COPD) pathogenesis. Aging-linked and cigarette smoke (CS)–induced functional deterioration of lysosomes may be associated with impaired autophagy. Lysosomal membrane permeabilization (LMP) is indicative of damaged lysosomes. Galectin-3 and tripartite motif protein (TRIM) 16 play a cooperative role in recognizing LMP and inducing lysophagy, a lysosome-selective autophagy, to maintain lysosome function. In this study, we sought to examine the role of TRIM16-mediated lysophagy in regulating CS-induced LMP and cellular senescence during COPD pathogenesis by using human bronchial epithelial cells and lung tissues. CS extract (CSE) induced lysosomal damage via LMP, as detected by galectin-3 accumulation. Autophagy was responsible for modulating LMP and lysosome function during CSE exposure. TRIM16 was involved in CSE-induced lysophagy, with impaired lysophagy associated with lysosomal dysfunction and accelerated cellular senescence. Airway epithelial cells in COPD lungs showed an increase in lipofuscin, aggresome and galectin-3 puncta, reflecting accumulation of lysosomal damage with concomitantly reduced TRIM16 expression levels. Human bronchial epithelial cells isolated from COPD patients showed reduced TRIM16 but increased galectin-3, and a negative correlation between TRIM16 and galectin-3 protein levels was demonstrated. Damaged lysosomes with LMP are accumulated in epithelial cells in COPD lungs, which can be at least partly attributed to impaired TRIM16-mediated lysophagy. Increased LMP in lung epithelial cells may be responsible for COPD pathogenesis through the enhancement of cellular senescence.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a66154d24217a9d7edc4a00831114336Test
https://pubmed.ncbi.nlm.nih.gov/34135057Test

المؤلفون: Akihiro Ichikawa, Yusuke Hosaka, Tsukasa Kadota, Akihiko Ito, Yu Fujita, Nayuta Saito, Takanori Numata, Masahiro Yoshida, Kazuyoshi Kuwano, Naoaki Watanabe, Hironori Kawamoto, Kazuya Tsubouchi, Jun Araya, Shunsuke Minagawa, Hiromichi Hara

المصدر: Mechanisms of lung injury and repair.

مصطلحات موضوعية: Gene knockdown, Programmed cell death, TUNEL assay, business.industry, Autophagy, Cell, respiratory system, digestive system, environment and public health, respiratory tract diseases, Transactivation, medicine.anatomical_structure, Apoptosis, medicine, Cancer research, Signal transduction, business

الوصف: Introduction: Cigarette smoke (CS) induces oxidative modifications with concomitant unfold protein response (UPR). Nrf2 is a transcription factor orchestrating the antioxidant defense system, thus Nrf2 can be a critical determinant of oxidative damage in COPD lungs with increased apoptosis associated with UPR. Nrf2 also activates chaperon-mediated autophagy (CMA), which is responsible for adapting the cell to stressed conditions. Although the participation of CMA-mediated apoptosis has been reported in COPD, mechanistic involvement of Nrf2-regulated CMA in COPD pathogenesis, especially in terms of UPR remains obscure. Methods: We used Beas-2B cells, primary human bronchial epithelial cells (HBEC), and lung tissues. CMA activity was evaluated by the expression levels of lysosomal associated membrane protein type 2a (LAMP2A). Cell death were assessed by LDH assay, TUNEL staining, and flow cytometry. ER stress-related signaling pathway was evaluated by western blotting. Results: CSE induced LAMP2A expression through Nrf2-mediated transactivation in HBEC, which was supported by Nrf2 knockdown. Nrf2 and LAMP2A knockdown enhanced UPR including CHOP accompanied by increased apoptosis during CSE exposure, which was reversed by LAMP2A overexpression. Immunohistochemistry showed that Nrf2 and LAMP2A levels were reduced in COPD compared with non-COPD lungs. Both Nrf2 and LAMP2A levels were reduced in HBEC isolated from COPD lungs and positive correlation between Nrf2 and LAMP2A expression levels was demonstrated. Conclusion: These findings suggest that functional crosstalk between CMA and UPR, and Nrf2-CMA axis is responsible for regulating CHOP-mediated apoptosis during COPD pathogenesis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::19801dadcfeafa9e830fd8169cf964baTest
https://doi.org/10.1183/13993003.congress-2020.608Test

المؤلفون: Kazuya Tsubouchi, Hideki Matsudaira, Jun Araya, Takashi Ohtsuka, Yu Fujita, Daisuke Takekoshi, Shunsuke Minagawa, Tsukasa Kadota, Mitsuo Hashimoto, Takanori Numata, Jun Hirano, Kazuyoshi Kuwano, Akihiro Ichikawa, Nayuta Saito, Saburo Ito, Akihiko Ito, Yusuke Hosaka, Hiromichi Hara, Hirofumi Utsumi, Keitaro Okuda, Katsutoshi Nakayama, Hiroshi Wakui, Shohei Mori, Naoaki Watanabe, Junko Watanabe, Masahiro Yoshida, Hironori Kawamoto

المصدر: Journal of immunology (Baltimore, Md. : 1950). 205(5)

مصطلحات موضوعية: NF-E2-Related Factor 2, Immunology, Cell, Apoptosis, Chaperone-Mediated Autophagy, environment and public health, digestive system, Pathogenesis, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Chaperone-mediated autophagy, Smoke, Tobacco, Immunology and Allergy, Medicine, Humans, Lung, health care economics and organizations, Cells, Cultured, Gene knockdown, business.industry, Autophagy, Epithelial Cells, humanities, respiratory tract diseases, medicine.anatomical_structure, Cancer research, Unfolded protein response, Unfolded Protein Response, business, Lysosomes, Homeostasis, 030215 immunology

الوصف: Cigarette smoke (CS) induces accumulation of misfolded proteins with concomitantly enhanced unfolded protein response (UPR). Increased apoptosis linked to UPR has been demonstrated in chronic obstructive pulmonary disease (COPD) pathogenesis. Chaperone-mediated autophagy (CMA) is a type of selective autophagy for lysosomal degradation of proteins with the KFERQ peptide motif. CMA has been implicated in not only maintaining nutritional homeostasis but also adapting the cell to stressed conditions. Although recent papers have shown functional cross-talk between UPR and CMA, mechanistic implications for CMA in COPD pathogenesis, especially in association with CS-evoked UPR, remain obscure. In this study, we sought to examine the role of CMA in regulating CS-induced apoptosis linked to UPR during COPD pathogenesis using human bronchial epithelial cells (HBEC) and lung tissues. CS extract (CSE) induced LAMP2A expression and CMA activation through a Nrf2-dependent manner in HBEC. LAMP2A knockdown and the subsequent CMA inhibition enhanced UPR, including CHOP expression, and was accompanied by increased apoptosis during CSE exposure, which was reversed by LAMP2A overexpression. Immunohistochemistry showed that Nrf2 and LAMP2A levels were reduced in small airway epithelial cells in COPD compared with non-COPD lungs. Both Nrf2 and LAMP2A levels were significantly reduced in HBEC isolated from COPD, whereas LAMP2A levels in HBEC were positively correlated with pulmonary function tests. These findings suggest the existence of functional cross-talk between CMA and UPR during CSE exposure and also that impaired CMA may be causally associated with COPD pathogenesis through enhanced UPR-mediated apoptosis in epithelial cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::201ab1241322fe0a4a4c043cd6bfb28bTest
https://pubmed.ncbi.nlm.nih.gov/32699159Test