scholarly journals Progesterone Aggravates Lung Fibrosis in a Mouse Model of Systemic Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Fatemeh Vafashoar ◽  
Kazem Mousavizadeh ◽  
Hadi Poormoghim ◽  
Amir Haghighi ◽  
Salar Pashangzadeh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Sclerosis ◽  
Serum Level ◽  
Mouse Model ◽  
Autoimmune Diseases ◽  
Lung Fibrosis ◽  
Normal Lung ◽  
Related Factors ◽  
Progesterone Treatment ◽  
Injured Lung

BackgroundGender-related factors have explained the higher prevalence of autoimmune diseases in women. Sex hormones play a key role in the immune system and parenchymal cells function; therefore, these hormones can be important in the pathogenesis of autoimmune diseases as a risk or beneficial factor. Lung fibrosis is the main cause of mortality in systemic sclerosis, a female predominant autoimmune disease. The objective of this study was to examine the effect of progesterone on lung fibrosis in a mouse model of systemic sclerosis.MethodsMice with bleomycin-induced lung fibrosis treated with progesterone subcutaneously for 21 and 28 days. Blood was collected for hormone and cytokine measurement at the end of treatment then, skin and lung tissues were harvested for histological assessment, gene expression, cytokine, hydroxyproline, and gelatinase measurement.ResultsTrichrome staining and hydroxyproline measurements showed that progesterone treatment increased the content of collagen in fibrotic and normal lung tissues. Progesterone increased α-SMA (P < 0.01), TGF- β (P < 0.05) and decreased MMP9 (P < 0.05) in fibrotic lung tissues. Also progesterone treatment decreased the gene expression of Col1a2 (P <0.05), Ctgf (P <01), End1 (0.001) in bleomycin- injured lung tissues. The serum level of TNF-α was decreased, but the serum level of cortisol was increased by progesterone treatment in fibrotic mice (P< 0.05).ConclusionOur results showed that progesterone aggravates lung fibrosis in a mouse model of systemic sclerosis.

scholarly journals Localisation of transforming growth factor β1 and β3 mRNA transcripts in normal and fibrotic human lung

Thorax ◽  
2001 ◽  
Vol 56 (7) ◽  
pp. 549-556
Author(s):  
R K Coker ◽  
G J Laurent ◽  
P K Jeffery ◽  
R M du Bois ◽  
C M Black ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Lung Tissue ◽  
Lung Fibrosis ◽  
Transforming Growth Factor ◽  
Human Lung ◽  
In Situ Hybridisation ◽  
Normal Lung ◽  
Gene And Protein Expression ◽  
Mrna Transcripts

BACKGROUNDTransforming growth factor β1 is implicated in the pathogenesis of lung fibrosis. It promotes extracellular matrix accumulation by increasing procollagen synthesis and reducing degradation. TGFβ1 gene and protein expression increase in experimental lung fibrosis, and TGFβ1 antibodies attenuate fibrosis in mice. The role of other TGFβ isoforms is unclear. This study aimed to localise TGFβ1 and TGFβ3 gene expression in fibrotic human lung and compare it with that in normal human lung.METHODSLung tissue from patients with cryptogenic fibrosing alveolitis and fibrosis associated with systemic sclerosis was examined by in situ hybridisation. Macroscopically normal lung from carcinoma resections was used as control tissue. Digoxigenin labelled riboprobes were synthesised from TGFβ isoform specific cDNA templates.RESULTSThe digoxigenin labelled riboprobes were sensitive and permitted precise cellular localisation of mRNA transcripts. TGFβ1 and TGFβ3 mRNA transcripts were widespread in normal lung and localised to alveolar macrophages and bronchiolar epithelium. TGFβ1 but not TGFβ3 mRNA was detected in mesenchymal and endothelial cells. In fibrotic lung tissue mRNA transcripts for both isoforms were also detected in metaplastic type II cells. TGFβ1 gene expression was enhanced in some patients. TGFβ3 was expressed in fibrotic lung but was not consistently altered compared with controls.CONCLUSIONTGFβ1mRNA transcripts were localised in normal and fibrotic human lung and TGFβ3 gene expression in human lung fibrosis was shown for the first time. The results suggest that TGFβ1 may play the predominant role in pathogenesis. It is suggested that TGFβ1 should be the primary target of anticytokine treatments for pulmonary fibrosis.

scholarly journals Differential Expression of Toll-Like Receptors 1 and 3 in Patients With Systemic Lupus Erythematosus and Systemic Sclerosis

2021 ◽  
Author(s):  
Ang-Jun Liu ◽  
Po-Chang Wu ◽  
Jian-Ruei Ciou ◽  
Pu-Wei Hou ◽  
Chung-Ming Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Systemic Sclerosis ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Housekeeping Genes ◽  
Toll Like Receptors ◽  
Systemic Lupus ◽  
Expression Levels ◽  
Significant Difference

Abstract Background: Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are autoimmune diseases with some overlapping clinical manifestations. Recent studies have revealed that Toll-like receptors (TLRs) play essential roles in autoimmune diseases' pathogenesis. To investigate the expression of TLR genes in SLE and SSc that are specific to the character of these diseases' pathogenesis.Methods: We recruited patients with SLE (n = 15) and SSc (n = 9) from China Medical University Hospital hospital in Taiwan from 2016 to 2017. Included were healthy reference controls and SLE datasets from the NCBI database. RNA was extracted from peripheral blood cells of the patients for next-generation sequencing (NGS). Results in identified differentially expressed genes were compared to explore TLRs' association with SLE and SSc pathogenesis. Housekeeping genes, including ACTB, GAPDH, PGK1, PPIB, SDHA, and TBP, were used to normalize the expression levels of the TLR genes. Results: There were significant differences in raw gene expression for patients with SLE and SSc (p < 0.05). No significant difference between patients with SLE and control datasets with SLE (p >0.05). The expression levels of TLR1 (p = 0.018) and TLR3 (p = 0.031) were significantly upregulated in the patients with SSc compared with those with SLE, normalized by GAPDH. Compared with many housekeeping genes, ACTB, GAPDH, and TBP indicated a significant difference (p < 0.05) in the expression of TLR1and TLR3. Conclusions: TLR1 and TLR3 can serve as biomarkers to distinguish the gene expression between SLE and SSc, normalized with housekeeping genes such as ACTB, GADPH, and TBP.

O04 In vivo assessment of prevention of lung fibrosis using the pan-PPAR agonist lanifibranor in the TbRIIDk-fib mouse model of systemic sclerosis

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_3) ◽  
Author(s):  
Emma Derrett-Smith ◽  
Xu Shi-Wen ◽  
David Abraham ◽  
Olivier Lacombe ◽  
Pierre Broqua ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Mouse Model ◽  
Lung Fibrosis ◽  
Ppar Agonist ◽  
In Vivo Assessment

scholarly journals The Effect of Dexamethasone on Bleomycin-Induced Lung Fibrosis in the Mouse Model of Systemic Sclerosis

2018 ◽  
Vol 12 (8) ◽  
pp. 86-94
Author(s):  
Salar PashangZadeh ◽  
Marjan Taherian ◽  
Fatemeh Vafashoar ◽  
Ali Anisian ◽  
Kazem Mousavizadeh ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Mouse Model ◽  
Lung Fibrosis

scholarly journals The pan-PPAR agonist lanifibranor reduces development of lung fibrosis and attenuates cardiorespiratory manifestations in a transgenic mouse model of systemic sclerosis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Emma Derrett-Smith ◽  
Kristina E. N. Clark ◽  
Xu Shiwen ◽  
David J. Abraham ◽  
Rachel K. Hoyles ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Systemic Sclerosis ◽  
Mouse Model ◽  
Right Ventricular ◽  
Lung Fibrosis ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Ppar Agonist ◽  
The Impact ◽  
Ppar Pathway

Abstract Background The TβRII∆k-fib transgenic (TG) mouse model of scleroderma replicates key fibrotic and vasculopathic complications of systemic sclerosis through fibroblast-directed upregulation of TGFβ signalling. We have examined peroxisome proliferator-activated receptor (PPAR) pathway perturbation in this model and explored the impact of the pan-PPAR agonist lanifibranor on the cardiorespiratory phenotype. Methods PPAR pathway gene and protein expression differences from TG and WT sex-matched littermate mice were determined at baseline and following administration of one of two doses of lanifibranor (30 mg/kg or 100 mg/kg) or vehicle administered by daily oral gavage up to 4 weeks. The prevention of bleomycin-induced lung fibrosis and SU5416-induced pulmonary hypertension by lanifibranor was explored. Results Gene expression data were consistent with the downregulation of the PPAR pathway in the TβRII∆k-fib mouse model. TG mice treated with high-dose lanifibranor demonstrated significant protection from lung fibrosis after bleomycin and from right ventricular hypertrophy following induction of pulmonary hypertension by SU5416, despite no significant change in right ventricular systolic pressure. Conclusions In the TβRII∆k-fib mouse strain, treatment with 100 mg/kg lanifibranor reduces the development of lung fibrosis and right ventricular hypertrophy induced by bleomycin or SU5416, respectively. Reduced PPAR activity may contribute to the exaggerated fibroproliferative response to tissue injury in this transgenic model of scleroderma and its pulmonary complications.

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