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Review
. 2023 Oct 26:14:1126661.
doi: 10.3389/fendo.2023.1126661. eCollection 2023.

Non-apoptotic programmed cell deaths in diabetic pulmonary dysfunction: the new side of advanced glycation end products

Yimin Dai #  1 , Shuang Zhou #  1 , Lin Qiao  1 , Zhao Peng  1 , Jiuliang Zhao  1 , Dong Xu  1 , Chanyuan Wu  1 , Mengtao Li  1 , Xiaofeng Zeng  1 , Qian Wang  1
Affiliations
Review

Non-apoptotic programmed cell deaths in diabetic pulmonary dysfunction: the new side of advanced glycation end products

Yimin Dai et al. Front Endocrinol (Lausanne). .

Abstract

Diabetes mellitus (DM) is a chronic metabolic disorder that affects multiple organs and systems, including the pulmonary system. Pulmonary dysfunction in DM patients has been observed and studied for years, but the underlying mechanisms have not been fully understood. In addition to traditional mechanisms such as the production and accumulation of advanced glycation end products (AGEs), angiopathy, tissue glycation, oxidative stress, and systemic inflammation, recent studies have focused on programmed cell deaths (PCDs), especially the non-apoptotic ones, in diabetic pulmonary dysfunction. Non-apoptotic PCDs (NAPCDs) including autophagic cell death, necroptosis, pyroptosis, ferroptosis, and copper-induced cell death have been found to have certain correlations with diabetes and relevant complications. The AGE-AGE receptor (RAGE) axis not only plays an important role in the traditional pathogenesis of diabetes lung disease but also plays an important role in non-apoptotic cell death. In this review, we summarize novel studies about the roles of non-apoptotic PCDs in diabetic pulmonary dysfunction and focus on their interactions with the AGE-RAGE axis.

Keywords: advanced glycosylation end products; diabetic pulmonary dysfunction; inflammation; non-apoptotic programmed cell deaths; oxidative stress.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Roles of autophagic cell death, pyroptosis, and necroptosis in the pathogenesis of diabetic lung disease. AGEs, advanced glycation end products; Akt, protein kinase; CML, Nϵ-carboxymethyl lysine; ERK, extracellular signal-related kinase; HMGB1, high-mobility group box 1; JAK, Janus Kinase; Ki-ras, Kirsten rat sarcoma viral oncogene; LPS, lipopolysaccharide; MEK, mitogen-activated protein kinases (MAPK) kinases; MLKL, mixed lineage kinase domain-like; mTORC1, mammalian target of rapamycin C1; NADPH, Nicotinamide Adenine Dinucleotide Phosphate Oxidase; NF-κB, nuclear factor kappa-B; NLRP3, Nod-like receptor protein 3; PI3K, phosphoinositide 3 kinase; PIPK, receptor interacting protein kinases; RAGE, AGE receptor; ROS, reactive oxygen species; STAT, signal transducer and activator of transcription; TNF-α, tumor necrosis factor-α; TNFR1, TNFα activating TNF receptor 1.
Figure 2
Figure 2
Roles of ferroptosis and cuproptosis in the pathogenesis of diabetic lung disease. AGEs, advanced glycation end products; ATF3, activating transcription factor 3; DLAT, dihydrolipoyl transacetylase; FDX1, ferredoxin 1; FPN, ferroportin; FTH1, ferritin heavy chain 1; GPX4, glutathione peroxidase 4; GSH, glutathione; HO-1, heme oxygenase 1; Keapl, Kelch-like ECH-associated protein 1; LIAS, lipoyl synthase; NOQ1, NADH dehydrogenase, quinone 1; Nrf2, nuclear factor erythroid 2-related factor 2; p38, p38 mitogen-activated protein kinases; RAGE, AGE receptor; ROS, reactive oxidative species; SLC3A2, Solute Carrier Family 3, Member 2; SLC7A11, Solute Carrier Family 7, Member 11; SLC31A1, high affinity copper uptake protein 1; SPI1, transcription factor PU; System Xc-, cysteine/glutamate transporter receptor; TF, transferrin; TGF-β, growth factor-β; TLR, Toll-like receptor.
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This study was supported by CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-005 and 2019-I2M-2-008), the Beijing Municipal Science and Technology Commission (Z201100005520025), National High Level Hospital Clinical Research Funding (2022-PUMCH-A-107, 2022-PUMCH-C-020), the National Natural Science Foundation of China (81471615, 81601430), and Fundamental Research Funds for the Central Universities (3332021006).