Progranulin protects lung epithelial cells from cigarette smoking‐induced apoptosis

Lee, Kyoung Young; Park, Soyoung; Park, Sunjoo; Hong, Gyong Hwa; Moon, Keun‐Ai; Kim, You‐Sun; Oh, Yeon Mok; Kwon, Hyouk‐Soo; Kim, Tae‐Bum; Moon, Hee‐Bom; Cho, You Sook

doi:10.1111/resp.13023

Cited by 18 publications

(23 citation statements)

References 30 publications

(70 reference statements)

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“…In our earlier study we showed that CS induces accumulation of damaged proteins and their ineffective degradation due to an inhibition of the proteasome (Somborac‐Bačura et al., ). In this study, we found an increase in expression of HSP70 and HSP32 after the incubation of A549 cells with CSE for 6 h, while levels of HSP70, HSP32 and HSP27 were up‐regulated at 8 h and remained elevated up to 48 h. Previous studies showed that CS increased the expression of HSP32 (HO‐1) in SA 3T3 mouse fibroblasts (Müller & Gebel, ), premonocytic U937 cell line (Favatier & Polla, ), A549 alveolar epithelial cells (Fukano, Oishi, Chibana, Numazawa, & Yoshida, ), BEAS‐2B bronchial epithelial cells (Lee et al., ; Li Y et al, 2016; Slebos et al., ), pulmonary fibroblasts (Baglole, Sime, & Phipps, ) and human bronchial smooth muscle cells (Jeong et al., ). Moreover, the induction of HO‐1 was associated with the formation of hydroxyl radicals that lowered the concentration of GSH in the cells (Baglole et al., ; Müller & Gebel, ).…”

Section: Discussionsupporting

confidence: 60%

“…Transfection of BEAS‐2B bronchial epithelial cells with adenovirus construct containing HO‐1 cDNA prevented cell death by increasing ATP levels (Slebos et al., ). Recently, it was shown that pretreating cells with neutrophil elastase suppressed the CSE‐induced expression of HO‐1 by cleaving sirtuin 1, indicating the importance of cross‐talk between oxidative stress and proteases in the pathogenesis of COPD (Lee et al., ). Reduced HO‐1 expression was found in alveolar macrophages of COPD patients compared to healthy smokers (Maestrelli et al., ); the authors suggested that patients with severe COPD had a reduced defence against oxidative stress as a consequence of the disease.…”

Section: Discussionmentioning

confidence: 99%

“…(HO-1) in SA 3T3 mouse fibroblasts (Müller & Gebel, 1994), premonocytic U937 cell line (Favatier & Polla, 2001), A549 alveolar epithelial cells (Fukano, Oishi, Chibana, Numazawa, & Yoshida, 2006), BEAS-2B bronchial epithelial cells (Lee et al, 2017;Li Y et al, 2016;Slebos et al, 2007), pulmonary fibroblasts (Baglole, Sime, & Phipps, 2008) and human bronchial smooth muscle cells (Jeong et al, 2012).…”

Section: Induction Of Hsps By Csementioning

confidence: 99%

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Differential expression of heat shock proteins and activation of mitogen‐activated protein kinases in A549 alveolar epithelial cells exposed to cigarette smoke extract

Bačura

Rumora

Novak

et al. 2018

Experimental Physiology

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New Findings What is the central question of this study?What is the effect of cigarette smoke on cell death, oxidative damage, expression of heat shock proteins (HSPs) and activation of mitogen‐activated protein kinases (MAPKs) in A549 alveolar epithelial cells? What is the main finding and its importance?Cigarette smoke induces cytotoxicity and oxidative damage to A549 cells, increases expression of different HSPs and activates MAPK signalling pathways. This could be related to inflammatory response and apoptosis observed in lungs of patients with smoking‐related diseases. Abstract Cigarette smoking is one of the main risk factors for development of chronic obstructive pulmonary disease (COPD). We previously reported that cigarette smoke (CS) induces damage to proteins and their ineffective degradation. Here, we hypothesize that CS could induce oxidative stress and cytotoxicity in lung epithelial cells through alterations of heat shock protein (HSP) expression and mitogen‐activated protein kinase (MAPK) signalling pathways. We exposed A549 alveolar epithelial cells to various concentrations of cigarette smoke extract (CSE). Higher concentrations of CSE caused apoptosis of A549 cells after 4 h, while after 24 h cell viability was decreased, and lactate dehydrogenase in cell culture medium was increased as well as the number of necrotic cells. Concentrations of malondialdehyde (MDA) were elevated, while total thiol groups were decreased. Changes in the expression of HSPs (HSP70, HSP32 and HSP27) were time‐dependent. After 6 h, CSE caused an increase in the expression of HSP70 and HSP32, while after 8 h all examined HSPs were up‐regulated and remained increased up to 48 h. Treatment of A549 cells with CSE stimulated phosphorylation of extracellular signal‐regulated kinase and p38 in a dose‐dependent manner, while c‐Jun N‐terminal kinase activation was not detected. By using specific inhibitors, we demonstrated that MAPKs and HSPs interplay in CSE effects. In conclusion, our results show that MAPKs and HSPs are involved in the mechanism underlying CSE‐induced cytotoxicity and oxidative damage to A549 alveolar epithelial cells. These processes could be related to inflammatory response and apoptosis observed in lungs of patients with smoking‐related diseases, such as COPD.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Induction Of Hsps By Csementioning

confidence: 99%

See 1 more Smart Citation

Differential expression of heat shock proteins and activation of mitogen‐activated protein kinases in A549 alveolar epithelial cells exposed to cigarette smoke extract

Bačura

Rumora

Novak

et al. 2018

Experimental Physiology

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“…Alveolar type II epithelial cells (AECII) play important role in the maintenance of normal lung structure and help the repair and recovery of the lung after biological and physical lung damages [5,6]. Cigarette smoking has been shown to cause the apoptosis of AECII [7].…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Induces HRD1 to Protect Alveolar Type II Epithelial Cells from Apoptosis Induced by Cigarette Smoke Extract

Tan

Jiang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Cigarette smoking is a major risk factor of chronic obstructive pulmonary disease. This study aimed to examine the effects of cigarette smoke extract (CSE) on alveolar type II epithelial cells (AECII) and investigate the underlying mechanism. Methods: Primary AECII were isolated from rat lung tissues and exposed to CSE. Apoptosis was detected by flow cytometry. Protein expression was detected by Western blot analysis. Results: Primary rat AECII maintained morphological and physiological characteristic after 3 passages. CSE increased the expression of ER specific pro-apoptosis factors CHOP and caspase 12, and the phosphorylation of JNK in AECII. CSE activated ER stress signaling and increased the phosphorylation of PERK, eIF2α and IRE1. Furthermore, CSE induced the expression of Hrd1, a key factor of ER-associated degradation, in AECII. Knockdown of Hrd1 led to more than 2 fold increase of apoptosis, while overexpression of Hrd1 attenuated CSE induced apoptosis of AECII. Conclusions: Our results suggest that ER stress induces HRD1 to protect alveolar type II epithelial cells from apoptosis induced by CSE.

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“…found that activation of the Smad pathway in bronchoscopic airway biopsies was linked to epithelial mesenchymal transition activity and loss of lung function. Lee et al . found that COPD patients exhibited significantly lower progranulin (PGRN) serum levels and higher peripheral blood mononuclear cells intracellular PGRN levels.…”

Section: Copdmentioning

confidence: 99%

Year in review 2017: Chronic obstructive pulmonary disease and asthma

Benton

Lim

et al. 2018

Respirology

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Progranulin protects lung epithelial cells from cigarette smoking‐induced apoptosis

Abstract: PGRN in airway epithelial cells may regulate CS-induced AEC apoptosis and may be involved in the development of COPD.

Cited by 18 publications

References 30 publications

Differential expression of heat shock proteins and activation of mitogen‐activated protein kinases in A549 alveolar epithelial cells exposed to cigarette smoke extract

Differential expression of heat shock proteins and activation of mitogen‐activated protein kinases in A549 alveolar epithelial cells exposed to cigarette smoke extract

Endoplasmic Reticulum Stress Induces HRD1 to Protect Alveolar Type II Epithelial Cells from Apoptosis Induced by Cigarette Smoke Extract

Year in review 2017: Chronic obstructive pulmonary disease and asthma

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