BAG3 Alleviates Atherosclerosis by Inhibiting Endothelial-to-Mesenchymal Transition via Autophagy Activation

Diao, Hongtao; Wu, Kaili; Lan, Dingming; Wang, Dongwei; Zhao, Jingjing; Huang, Bingying; Shao, Xiaoqi; Wang, Ruonan; Tan, Huiling; Tang, Xinyuan; Yan, Meiling; Zhang, Yue

doi:10.3390/genes13081338

Cited by 10 publications

(4 citation statements)

References 53 publications

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“…HSPB8 forms a dimer that binds with the cochaperone protein BAG3 associated with HSP70. BAG3 activates autophagy by synthesizing a cochaperone-assisted selective autophagy (CASA) complex with HSP70 and HSPB8, thereby inhibiting a series of molecular events that cause vascular endothelial dysfunction and thus alleviate atherosclerosis [25]. A recent study con rmed the diagnostic value of HSPB8 in AS patients.…”

Section: Discussionmentioning

confidence: 99%

A diagnostic model for atherosclerosis established on the basis of autophagy-related genes

He,

Wang,

Liu

et al. 2024

Preprint

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Background Atherosclerosis, a common cardiovascular disease, has a complex etiology. In recent years, autophagy has been recognized to play a significant role in the development of atherosclerosis. This study aimed to establish a diagnostic model for atherosclerosis based on autophagy-related genes. Objectives Our research aims to establish a diagnostic model for atherosclerosis based on autophagy-related genes. Methods GSE100927 and GSE28829 were downloaded from the GEO website (https:// www. ncbi. nlm. nih. gov/ geo/). Autopophagy-related genes were obtained from the Human Autophagy Database (HADb) database (http://www.autophagy.lu/index.html). Then, taking the intersection, we obtained 19 differentially expressed autophagy-related genes. Using machine learning methods and validation with GSE28829, we identified six genes. These six genes were used to construct a new diagnostic model for arteriosclerosis, and a nomogram was generated. Results The results demonstrated that the new model exhibited good accuracy and sensitivity in diagnosing atherosclerosis. Additionally, we explored the role of these six genes in 28 types of immune cells through immune infiltration analysis. Furthermore, we validated the differential expression of the diagnostic model in normal mice and mice with atherosclerosis through in vivo experiments. Conclusion We successfully established a diagnostic model for atherosclerosis based on autophagy-related genes. This model provides new insights and methods for the early diagnosis and treatment of atherosclerosis. This research is expected to lead to the development of new strategies for the prevention and treatment of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

A diagnostic model for atherosclerosis established on the basis of autophagy-related genes

He,

Wang,

Liu

et al. 2024

Preprint

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“…In recent years, the function of Bag3 in cellular autophagy has gained increasing attention [34,35]. This study focuses on exploring the role of BAG3-mediated autophagy in knee OA.…”

Section: Discussionmentioning

confidence: 99%

Bag3 protects chondrocytes and alleviates osteoarthritis by restoring autophagy flux

Lin

et al. 2023

Preprint

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Objective Chondrocyte apoptosis resulting from the inhibition of autophagic flux is a significant contributor to Osteoarthritis (OA). In recent years, there has been increasing interest in the role of Bcl-2-associated athanogene 3 (Bag3) in autophagy; however, its specific contribution to the pathogenesis of knee osteoarthritis remains unclear.Methods X-ray imaging and tissue staining techniques were used to evaluate the radiographic and histomorphological features of the mouse knee joint. Western blotting was employed to analyze gene and protein expression levels in an in vitro setting. Immunofluorescence staining was utilized to identify and visualize specific proteins in the tissue samples. Knockdown and overexpression techniques were employed to manipulate the expression level of BAG3, a protein of interest. DMM (destabilization of the medial meniscus) was used to induce osteoarthritis in mice for studying the effects of Bag3 overexpression on OA development.Results The results of these experiments showed that in mouse knee OA tissue, BAG3 was upregulated compared to healthy tissue. Knockdown and overexpression experiments of BAG3 revealed a potential anti-apoptotic and autophagy-enhancing function of BAG3 in the context of osteoarthritis. CQ treatment reversed BAG3-induced chondrocyte protection under oxidative stress. Bag3 overexpression ameliorated DMM-induced OA development in mice.Conclusion Bag3 alleviates chondrocytes apoptosis by protecting autophagic flux, thereby improving OA.

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“…In renal tubular cells, HSPB1 also increases LC3-II protein levels and decreases SQSTM1/p62 protein levels [87]. HSPB8 participates in autophagy as a component of the chaperone-assisted selective autophagy (CASA) complex, and CASA is a form of macroautophagy that initiates the ubiquitin-dependent autophagic sorting of damaged proteins for lysosomal degradation [51,119,120]. The CASA complex consists of HSP70, HSPB8, and Bcl-2-associated athanogene 3 (BAG3), the latter of which is a co-chaperone that regulates the ATPase activity of HSP70 and also serves as a scaffold to link HSP70 to HSPB8 [121][122][123].…”

Section: Shsps Promote Autophagymentioning

confidence: 99%

Functional Diversity of Mammalian Small Heat Shock Proteins: A Review

Fan

2023

Cells

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The small heat shock proteins (sHSPs), whose molecular weight ranges from 12∼43 kDa, are members of the heat shock protein (HSP) family that are widely found in all organisms. As intracellular stress resistance molecules, sHSPs play an important role in maintaining the homeostasis of the intracellular environment under various stressful conditions. A total of 10 sHSPs have been identified in mammals, sharing conserved α-crystal domains combined with variable N-terminal and C-terminal regions. Unlike large-molecular-weight HSP, sHSPs prevent substrate protein aggregation through an ATP-independent mechanism. In addition to chaperone activity, sHSPs were also shown to suppress apoptosis, ferroptosis, and senescence, promote autophagy, regulate cytoskeletal dynamics, maintain membrane stability, control the direction of cellular differentiation, modulate angiogenesis, and spermatogenesis, as well as attenuate the inflammatory response and reduce oxidative damage. Phosphorylation is the most significant post-translational modification of sHSPs and is usually an indicator of their activation. Furthermore, abnormalities in sHSPs often lead to aggregation of substrate proteins and dysfunction of client proteins, resulting in disease. This paper reviews the various biological functions of sHSPs in mammals, emphasizing the roles of different sHSPs in specific cellular activities. In addition, we discuss the effect of phosphorylation on the function of sHSPs and the association between sHSPs and disease.

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BAG3 Alleviates Atherosclerosis by Inhibiting Endothelial-to-Mesenchymal Transition via Autophagy Activation

Cited by 10 publications

References 53 publications

A diagnostic model for atherosclerosis established on the basis of autophagy-related genes

A diagnostic model for atherosclerosis established on the basis of autophagy-related genes

Bag3 protects chondrocytes and alleviates osteoarthritis by restoring autophagy flux

Functional Diversity of Mammalian Small Heat Shock Proteins: A Review

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