Phosphorylated STAT3 suppresses microRNA‐19b/1281 to aggravate lung injury in mice with type 2 diabetes mellitus‐associated pulmonary tuberculosis

Wang, Xianhua; Lin, Yuefu; Liang, Ying; Yang, Yankun; Wang, Dong; Tai, Aer; Wu, Shuimiao; Pan, Jian

doi:10.1111/jcmm.15954

Cited by 14 publications

(13 citation statements)

References 44 publications

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“…Streptozotocin (STZ) was dissolved in 50 mmol/L citrate buffer, and 180 mg/kg mixed solution was intraperitoneally injected into mice for three times at a 10-day interval. The mice were intraperitoneally injected with 60 mg/kg nicotinamide dissolved in saline water 15 min prior to the STZ injection [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

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Sp1 transcription factor represses transcription of phosphatase and tensin homolog to aggravate lung injury in mice with type 2 diabetes mellitus-pulmonary tuberculosis

et al. 2022

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Type 2 diabetes mellitus (T2DM) can enhance the risk of mycobacterium tuberculosis (Mtb) infection and aggravate pulmonary tuberculosis (PTB). This study intended to explore the function of phosphatase and tensin homolog (PTEN) in T2DM-PTB and the molecules involved. Mice were treated with streptozotocin to induce T2DM and then infected with Mtb. The mice with T2DM had increased weight, blood glucose level, glucose intolerance and insulin resistance, and increased susceptibility to PTB after Mtb infection. PTEN was significantly downregulated in mice with T2DM-PTB and it had specific predictive value in patients. Overexpression of PTEN improved mouse survival and reduced bacterial load, inflammatory infiltration, cell apoptosis, and fibrosis in lung tissues. Sp1 transcription factor (SP1) was predicted and identified as an upstream regulator of PTEN. SP1 suppressed PTEN transcription. Silencing of SP1 enhanced mouse survival and alleviated the lung injury, and it promoted the M1 polarization of macrophages in murine lung tissues. However, further downregulation of PTEN increased protein kinase B (Akt) phosphorylation and blocked the alleviating roles of SP1 silencing in T2DM-PTB. This study demonstrates that SP1 represses PTEN transcription to promote lung injury in mice with T2DM-PTB through Akt activation.

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Section: Methodsmentioning

confidence: 99%

“…The compressed air was adjusted to 5 L/min, and the main air flow was approximately 28 L/min (1 cfm). After 30 min of atomization, the mice were disinfected and treated with the aerosol [ 23 ].…”

Section: Methodsmentioning

confidence: 99%

Sp1 transcription factor represses transcription of phosphatase and tensin homolog to aggravate lung injury in mice with type 2 diabetes mellitus-pulmonary tuberculosis

et al. 2022

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“…One month after STZ injection, the T2DM mice were treated with MTB. H37Rv (ATCC, USA) for PTB induction [ 29 , 30 ]. The H37Rv was diluted in PBS to 2 × 10 6 colony‐forming units (CFU)/mL, and then it was atomized by an atomizer.…”

Section: Methodsmentioning

confidence: 99%

Ginsenoside Rg1 Inhibits STAT3 Expression by miR-15b-5p to Attenuate Lung Injury in Mice with Type 2 Diabetes Mellitus-Associated Pulmonary Tuberculosis

Mao

Meng

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Type 2 diabetes mellitus (T2DM) has been regarded as a critical risk factor for pulmonary tuberculosis (PTB). Ginsenoside Rg1 has been identified as a potential therapeutic agent for T2DM by suppressing the inflammatory response. However, the effect of Rg1 on T2DM-associated PTB has not been reported. In this study, we aimed to explore the function of Rg1 in the regulation of T2DM-associated PTB. We established a T2DM-associated PTB mouse model and found that the fibrosis of lung tissues was inhibited by Rg1 in T2DM-associated PTB mice. The lung injury of T2DM-associated PTB mice was repressed by Rg1. Moreover, the levels of IL-6, TNF-α, and IL-1β in the lung tissues and serum were decreased by Rg1 in T2DM-associated PTB mice. The treatment with Rg1 inhibited the levels of free fatty acid and enhanced the expression of miR-15b-5p in lung tissues of T2DM-associated PTB mice. MiR-15b-5p targeted and inhibited the STAT3 expression. The expression of STAT3 was downregulated by Rg1, while the inhibition of miR-15b-5p reversed the downregulation. The expression of miR-15b-5p was reduced, but the expression of STAT3 was upregulated in the lung tissues of T2DM-associated PTB mice. We validated that miR-15b-5p attenuated inflammation and lung injury in the T2DM-associated PTB mouse model. The overexpression of STAT3 or the suppression of miR-15b-5p restored lung fibrosis and injury inhibited by Rg1 in T2DM-associated PTB mice. Meanwhile, the Rg1-repressed levels of IL-6, TNF-α, and IL-1β were enhanced by the overexpression of STAT3 or the suppression of miR-15b-5p. In addition, the levels of free fatty acid repressed by Rg1 were reversed by STAT3 overexpression and miR-15b-5p inhibition. Thus, we conclude that ginsenoside Rg1 inhibits the STAT3 expression by miR-15b-5p to attenuate lung injury in mice with type 2 diabetes mellitus-associated pulmonary tuberculosis.

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“…On the other hand, diabetic disease will further increase the severity of pulmonary TB if the impaired glucose tolerance impairments cannot be controlled [ 4 ]. Type-II DM is regarded as an important factor in the development and progression of pulmonary TB [ 2 , 5 ]. Radiological presentation (computed tomography, CT) revealed the increase in the number and size of cavities in the lower lung part in TB patients with DM than the patients without DM [ 3 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

The relationship between computed tomography appearance of pulmonary tuberculosis and blood glucose levels in 763 diabetes mellitus patients with pulmonary tuberculosis: a comparative study

Ren

Tian

et al. 2022

Endocrine

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Introduction Glucose tolerance is often impaired in pulmonary tuberculosis (TB) patients. We aimed to explore the relationship between computed tomography (CT) findings of TB and blood glucose levels in diabetes mellitus (DM) patients. Methods 763 diabetes mellitus patients with pulmonary tuberculosis (DMTB) from March 2015 to March 2018 were selected and their clinical data were retrospectively evaluated. CT appearance of DMTB was reviewed and compared according to blood glucose levels and CT scores. TB scores were calculated according to the combination of typical and atypical CT appearance. The relationship between blood glucose levels and CT scores was analyzed via Pearson correlation coefficient. Results TB lesions mainly occurred in the left lung and the lower lobes in the DMTB patients. Nodules and cavities are the main typical complications in these DMTB patients, and especially the number and size of cavities predominantly contribute to CT scan scores. The size of cavities (diameters (cm), median (95% CI of median)) was 0.72 (0.66–0.77), 1.20 (1.09–1.28), and 3.45 (2.92–3.94) from the low-, middle- and high-CT-score groups, respectively. The patients with high CT scores had a higher level of fasting plasma glucose (mean 13.48 mM, 95% CI of median 12.56–14.44 mM) than the patients in the low-CT-score (mean 8.73 mM, 95% CI of median 8.49–9.36 mM) and middle-CT-score groups (mean 10.16 mM, 95% CI of median 9.89–10.49 mM) (P < 0.0001). CT scores have a consistent relationship with the levels of blood glucose (rho = 0.60, P < 0.0001). Conclusions CT appearance stands for the severity of tuberculosis and is closely associated with blood glucose levels in diabetic TB patients.

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Phosphorylated STAT3 suppresses microRNA‐19b/1281 to aggravate lung injury in mice with type 2 diabetes mellitus‐associated pulmonary tuberculosis

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 14 publications

References 44 publications

Sp1 transcription factor represses transcription of phosphatase and tensin homolog to aggravate lung injury in mice with type 2 diabetes mellitus-pulmonary tuberculosis

Sp1 transcription factor represses transcription of phosphatase and tensin homolog to aggravate lung injury in mice with type 2 diabetes mellitus-pulmonary tuberculosis

Ginsenoside Rg1 Inhibits STAT3 Expression by miR-15b-5p to Attenuate Lung Injury in Mice with Type 2 Diabetes Mellitus-Associated Pulmonary Tuberculosis

The relationship between computed tomography appearance of pulmonary tuberculosis and blood glucose levels in 763 diabetes mellitus patients with pulmonary tuberculosis: a comparative study

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