αvβ3 Integrin as a Link between the Development of Fibrosis and Thyroid Hormones in Systemic Sclerosis

Kohon, Maia Yamila; Levy, Mor Zaaroor; Hornik-Lurie, Tzipi; Shalom, Avshalom; Berl, Ariel; Drucker, Liat; Levy, Yair; Matalon, Shay

doi:10.3390/ijms24108927

Cited by 3 publications

(1 citation statement)

References 61 publications

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“…Recently, αvβ3 integrin has been identified as a crucial link between fibrosis development and thyroid hormones (THs) in SSc. The finding suggest that the integrin exerts its function by deregulating THs binding site regulation 25 . Previous studies have demonstrated elevated levels of the Th1 chemokine CXCL10 in serum or tissue, which may play a key factor in systemic rheumatologic diseases 26 .…”

Section: Discussionmentioning

confidence: 99%

Negative causal exploration of systemic sclerosis: a Mendelian randomization analysis

Han,

Wang

et al. 2024

Sci Rep

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Systemic sclerosis (SSc), also known as scleroderma, is an autoimmune-related connective tissue disease with a complex and unknown pathophysiological mechanism with genes association. Several articles have reported a high prevalence of thyroid disease in SSc patients, while one study suggested a potential contribution of appendicitis to the development of SSc. To investigate this causal association, we conducted Mendelian randomization (MR) analysis using instrumental variables (IVs) to assess exposure and outcome. In the MR study involving two cohorts, all analyses were conducted using the TwoSampleMR package in R (version 4.3.0). Single nucleotide polymorphisms (SNPs) meeting a statistically significant threshold of 5E−08 were included in the analysis. Multiple complementary approaches including MR-IVW, MR-Egger, weighted median, simple mode, and weighted mode were employed to estimated the relationship between the exposure and outcome. Leave-one-out analysis and scatter plots were utilized for further investigation. Based on the locus-wide significance level, all of the MR analysis consequences manifested no causal association between the risk of appendicitis with SSc (IVW OR 0.319, 95% CI 0.063–14.055, P = 0.966). Negative causal effects of autoimmune thyroiditis (AT) on SSc (IVW OR 0.131, 95% CI 0.816–1.362, P = 0.686), Graves’ disease (GD) on SSc (IVW OR 0.097, 95% CI 0.837–1.222, P = 0.908), and hypothyroidism on SSc (IVW OR 1.136, 95% CI 0.977–1.321, P = 0.096) were derived. The reverse MR revealed no significant causal effect of SSc on thyroid disease. According to the sensitivity analysis, horizontal pleiotropy was unlikely to distort the causal estimates. The consequences indicated no significant association between AT, GD, and hypothyroidism with SSc. Similarly, there was no observed relationship with appendicitis.

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Section: Discussionmentioning

confidence: 99%

Negative causal exploration of systemic sclerosis: a Mendelian randomization analysis

Han,

Wang

et al. 2024

Sci Rep

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Assessing the impact of triiodothyronine treatment on the lung microbiome of mice with pulmonary fibrosis

Guo,

Xu,

Wang

et al. 2024

BMC Pulm Med

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Assessing the Impact of Triiodothyronine Treatment on the Lung Microbiome of Mice with Pulmonary Fibrosis

Guo,

Xu,

Wang

et al. 2023

Preprint

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Background Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by progressive pulmonary fibrosis (PF) exacerbation. IPF primarily affects older individuals and can lead to respiratory failure. This study aimed to assess the effects of triiodothyronine (T3) treatment on the lung microbiome of mice with PF. Methods Mice were perfused with bleomycin (BLM) to establish a PF model. Using a randomized design, 40 female specific pathogen-free (SPF) C57BL6/N mice were divided into four groups: saline, saline + T3, BLM, and BLM + T3. Hematoxylin and eosin and Masson’s trichrome staining were used to detect histological morphology, and 16S rRNA microbial sequencing was used to identify lung bacteria. An Enzyme-Linked Immunosorbent Assay was used to measure total T3(TT3), free T3(FT3, and reverse T3(rT3) levels in the peripheral serum. Results T3treatment ameliorated BLM-induced lung fibrosis and structural damage. The microbiome experienced a decrease in the abundance of Proteobacteria, Bacteroides, and Actinomycetes and an increase in the abundance of Firmicutes when exposed to BLM; however, T3treatment reversed this effect. The four groups showed no significant difference in alpha and beta microbiome diversity (P > 0.05), and the effect of T3treatment and BLM treatment on lung microbial alpha diversity was in the opposite direction, which was of positive significance; beta-diversity analysis suggested a relatively stable microbiome). Serum concentrations of TT3and FT3were positively correlated with microbiome abundance (P < 0.05). Administration of T3enhanced the microbiota in PF without affecting the diversity and biological functions of the microbiome (P > 0.05). Conclusion T3treatment had a positive effect on the lung microbiome of mice with PF. This finding partially supports the use of T3as a potential drug for the treatment of PF.

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αvβ3 Integrin as a Link between the Development of Fibrosis and Thyroid Hormones in Systemic Sclerosis

Cited by 3 publications

References 61 publications

Negative causal exploration of systemic sclerosis: a Mendelian randomization analysis

Negative causal exploration of systemic sclerosis: a Mendelian randomization analysis

Assessing the impact of triiodothyronine treatment on the lung microbiome of mice with pulmonary fibrosis

Assessing the Impact of Triiodothyronine Treatment on the Lung Microbiome of Mice with Pulmonary Fibrosis

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