SerpinA3g participates in the antiadipogenesis and insulin-resistance induced by tumor necrosis factor-α in 3T3-F442A cells

Salazar‐Olivo, Luis A.; Mejía-Elizondo, Rebeca; Alonso-Castro, Ángel Josabad; Ponce-Noyola, Patricia; Maldonado-Lagunas, Vilma; Meléndez-Zajgla, Jorge; Saavedra-Alanís, Víctor

doi:10.1016/j.cyto.2014.05.025

Cited by 12 publications

(8 citation statements)

References 52 publications

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“…In addition, Gornicka et al reported that the serine protease cathepsin B (CTSB) was upregulated in the adipose tissue of obese mice, [42] and SERPINA3 inhibited CTSB in adipocytes and was capable of suppressing the development of obesity. [43] In the present study, we found that A. muciniphila is able to upregulate the protein expression of SERPINA3 family proteins during adipogenesis, which may have anti-obesity effects on adipocytes. In particular, A. muciniphila highly overexpressed SERPINA3G in 3T3-L1 cells.…”

Section: Inhibitory Effects Of Overexpressed Serpina3g Protein On Lipid Accumulation In 3t3-l1 Cells Following Treatment With the Cell Lysupporting

confidence: 56%

“…Previous work has shown that SERPINA3G plays a role in the inhibition of cathepsin K (CTSK). [43,44] CTSK protein abundance and mRNA expression level in adipose tissue of overweight people were relatively higher than those in normal weight people. [45] Moreover, the production of TAG in 3T3-L1 cells was reduced after a treatment with a CTSK inhibitor.…”

Section: Inhibitory Effects Of Overexpressed Serpina3g Protein On Lipid Accumulation In 3t3-l1 Cells Following Treatment With the Cell Lymentioning

confidence: 84%

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An integrative multiomics approach to characterize anti‐adipogenic and anti‐lipogenic effects of Akkermansia muciniphila in adipocytes

Lee

Song

Lim

et al. 2021

Biotechnology Journal

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The cellular components of Akkermansia muciniphila are considered potential biotherapeutics for the improvement of obesity, diabetes, and metabolic diseases. However, the molecular-based mechanism of A. muciniphila for treatment of obesity, which can provide important evidence for human research, has rarely been explored. Here, we applied integrative multiomics approaches to investigate the underlying molecular mechanism involved in obesity treatment by A. muciniphila. First, the treatment with a cell lysate of A. muciniphila reduced lipid accumulation in 3T3-L1 cells and downregulated the mRNA expression of proteins involved in adipogenesis and lipogenesis.Our proteomic results revealed that A. muciniphila decreased the expression of proteins involved in fat cell differentiation, fatty acid metabolism, and energy metabolism in adipocytes. Moreover, A. muciniphila significantly reduced the level of metabolites related to glycolysis, the TCA cycle, and ATP in adipocytes. Interestingly, serine protease inhibitor A3 (SERPINA3) homologs were overexpressed in the 3T3-L1 cells treated with A. muciniphila. Small interfering RNA (siRNA) transfection demonstrated that A. muciniphila upregulates SERPINA3G expression and inhibits lipogenesis in adipocytes. Taken together, our multiomics-based approaches enabled to uncover the molecular mechanism of A. muciniphila for treatment of obesity and provide potent anti-lipogenic agents.

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Section: Inhibitory Effects Of Overexpressed Serpina3g Protein On Lipid Accumulation In 3t3-l1 Cells Following Treatment With the Cell Lysupporting

confidence: 56%

Section: Inhibitory Effects Of Overexpressed Serpina3g Protein On Lipid Accumulation In 3t3-l1 Cells Following Treatment With the Cell Lymentioning

confidence: 84%

An integrative multiomics approach to characterize anti‐adipogenic and anti‐lipogenic effects of Akkermansia muciniphila in adipocytes

Lee

Song

Lim

et al. 2021

Biotechnology Journal

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“…Consistently, RNA sequencing from the lungs of Ad5-hACE2 vs Ad5-empty mice at 3 DPI revealed that interferon (Ifn)-gamma and alpha, allograft rejection, complement and KRAS signaling are upregulated in response to SARS-CoV-2-infection ( Supplemental Figure 2A ). Interestingly, KRAS signaling components that are upregulated in SARS-CoV-2 infected mice ( Supplemental Figure 2B ), such as complement factor B (cfb), Sperpina and GPNMB and CTSS, mediate activity of various pro-inflammatory molecules such as TNF-α and are involved in endothelial activation and angiogenesis ( Hu et al., 2013 ; Salazar-Olivo et al., 2014 ; Rathi et al., 2017 ; Ni et al., 2020 ). These molecules may also contribute to endothelial activation and migration, which results in the increased vascular permeability that is the hallmark of fluid leakage and extravasation of inflammatory cells in the lungs of COVID-19 patients.…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 Infects Endothelial Cells In Vivo and In Vitro

Liu

Han

Blair

et al. 2021

Front. Cell. Infect. Microbiol.

119

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SARS-CoV-2 infection can cause fatal inflammatory lung pathology, including thrombosis and increased pulmonary vascular permeability leading to edema and hemorrhage. In addition to the lung, cytokine storm-induced inflammatory cascade also affects other organs. SARS-CoV-2 infection-related vascular inflammation is characterized by endotheliopathy in the lung and other organs. Whether SARS-CoV-2 causes endotheliopathy by directly infecting endothelial cells is not known and is the focus of the present study. We observed 1) the co-localization of SARS-CoV-2 with the endothelial cell marker CD31 in the lungs of SARS-CoV-2-infected mice expressing hACE2 in the lung by intranasal delivery of adenovirus 5-hACE2 (Ad5-hACE2 mice) and non-human primates at both the protein and RNA levels, and 2) SARS-CoV-2 proteins in endothelial cells by immunogold labeling and electron microscopic analysis. We also detected the co-localization of SARS-CoV-2 with CD31 in autopsied lung tissue obtained from patients who died from severe COVID-19. Comparative analysis of RNA sequencing data of the lungs of infected Ad5-hACE2 and Ad5-empty (control) mice revealed upregulated KRAS signaling pathway, a well-known pathway for cellular activation and dysfunction. Further, we showed that SARS-CoV-2 directly infects mature mouse aortic endothelial cells (AoECs) that were activated by performing an aortic sprouting assay prior to exposure to SARS-CoV-2. This was demonstrated by co-localization of SARS-CoV-2 and CD34 by immunostaining and detection of viral particles in electron microscopic studies. Moreover, the activated AoECs became positive for ACE-2 but not quiescent AoECs. Together, our results indicate that in addition to pneumocytes, SARS-CoV-2 also directly infects mature vascular endothelial cells in vivo and ex vivo, which may contribute to cardiovascular complications in SARS-CoV-2 infection, including multipleorgan failure.

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“…However, NOD mice contain over 30 other diabetic susceptibility genes that contribute to the development of autoimmunity(24). Of interest, in salivary gland, several genes that were suppressed by anti-CD40L are genes that have been reported to be associated with T1D and/or insulin regulation including Serpina3g (71), Iapp (72), Maf (73), and Igfbp5 where Igfbp5 is contained within IDDM13 susceptibility locus (74). …”

Section: Discussionmentioning

confidence: 99%

Autoimmune manifestations in aged mice arise from early-life immune dysregulation

Mahmoud¹,

Wang²,

Karnell³

et al. 2016

Sci. Transl. Med.

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Autoantibodies can be present years to decades prior to the onset of disease manifestations in autoimmunity. This suggests that the initial autoimmune trigger involves a peripheral lymphoid component, which ultimately drives disease pathology in local tissues later in life. Here we show Sjögren’s Syndrome manifestations that develop in aged NOD.H-2h4 mice were driven by and dependent on peripheral dysregulation that arose in early life. Specifically, elimination of spontaneous germinal centers in spleens of young NOD.H-2h4 mice by transient blockade of CD40 ligand (CD40L) or splenectomy abolished Sjögren’s pathology of aged mice. Strikingly, a single injection of anti-CD40L at 4 weeks-of-age prevented tertiary follicle neogenesis and greatly blunted the formation of key autoantibodies implicated in glandular pathology, including anti-muscarinic receptor antibodies. Microarray profiling of the salivary gland characterized the expression pattern of genes that increased with disease progression and showed early anti-CD40L greatly repressed B cell function, while having a broader effect on multiple biological pathways including IL-12 and interferon signaling. Importantly, a single, prophylactic treatment with anti-CD40L also inhibited the development of autoimmune thyroiditis and diabetes in NOD.H-2h4 and NOD mice, respectively, supporting a key role for CD40L in the pathophysiology of several autoimmune models. These results strongly suggest early peripheral immune dysregulation gives rise to autoimmune manifestations later in life and for diseases pre-dated by autoantibodies, early prophylactic intervention with biologics may prove efficacious.

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SerpinA3g participates in the antiadipogenesis and insulin-resistance induced by tumor necrosis factor-α in 3T3-F442A cells

Cited by 12 publications

References 52 publications

An integrative multiomics approach to characterize anti‐adipogenic and anti‐lipogenic effects of Akkermansia muciniphila in adipocytes

An integrative multiomics approach to characterize anti‐adipogenic and anti‐lipogenic effects of Akkermansia muciniphila in adipocytes

SARS-CoV-2 Infects Endothelial Cells In Vivo and In Vitro

Autoimmune manifestations in aged mice arise from early-life immune dysregulation

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