Maria Trojanowska's research while affiliated with Boston University and other places

Publications (226)

Preprint
Objective To evaluate the levels of periostin in patients with systemic sclerosis (SSc) and their association with features of systemic sclerosis. Methods The levels of periostin were assessed in the serum of 106 SSc patients and 14 healthy controls, and by immunofluorescence staining in cardiac tissue from 4 SSc patients and 4 healthy controls. Se...
Article
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Objective: The development of precision therapeutics for systemic sclerosis (SSc) has been hindered by the lack of models that accurately mimic the disease in vitro. Here we describe an all human self-assembled skin equivalent (saSE) system that recapitulates the crosstalk between macrophages and fibroblasts in cutaneous fibrosis. Methods: SSc a...
Article
Rationale: Fetal growth and survival depend critically on proper development and integrity of the vascular system. Fli1 (Friend leukemia integration 1), a member of the Ets family of transcription factors, plays critical roles in vascular morphogenesis and homeostasis at mid-gestation, the developmental stage at which expression of its upstream reg...
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Background Aldehyde dehydrogenase 1 family member A1 (RALDH1)-producing dermal dendritic cells (DCs), a conventional DC subset regulating skin fibrosis, are decreased in the involved skin of patients with systemic sclerosis (SSc). In this study, we investigated the contribution of Fli1 deficiency, a potential predisposing factor of SSc, to the phen...
Article
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Microvascular injury is considered an initial event in the pathogenesis of scleroderma and endothelial cells are suspected of being the target of the autoimmune process seen in the disease. EBV has long been proposed as a trigger for autoimmune diseases, including scleroderma. Nevertheless, its contribution to the pathogenic process remains poorly...
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Objectives: FLI1 and ERG, important regulators of endothelial cell homeostasis, are reduced in microvascular endothelial cells (MVEC) in scleroderma patients and their deficiency has been implicated in disease pathogenesis. The goal of this study was to identify the mechanisms involved in the protein turnover of FLI1 and ERG in MVECs. Methods: T...
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Background: Scleroderma (SSc) is a rare autoimmune disease characterized by vascular impairment and progressive fibrosis of the skin and other organs. Oncostatin M, a member of the IL-6 family, is elevated in SSc serum and was recognized as a significant player in various stages of fibrosis. The goal of this study was to assess the contribution of...
Article
Objective We previously established a new animal model (Klf5 +/‐;Fli1 +/‐ mice) broadly recapitulating fundamental pathologic features of systemic sclerosis (SSc). SSc vasculopathy is believed to occur as a result of impaired vascular remodeling, but its detailed mechanism has remained unknown. To address this issue, we investigated the properties...
Article
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Scleroderma (SSc) is an autoimmune connective tissue disease characterized by immune dysregulation, vasculopathy, and fibrosis. We have previously demonstrated that low Fli1 expression in SSc fibroblasts and endothelial cells plays an important role in SSc pathogenesis. Cells of myeloid and lymphoid origin also express Fli1 and are dysregulated in...
Preprint
Background Scleroderma (SSc) is a rare autoimmune disease characterized by vascular impairment and progressive fibrosis of the skin and other organs. Oncostatin M, a member of the IL-6 family, is elevated in SSc serum and was recognized as a significant player in various stages of fibrosis. The goal of this study was to assess the contribution of t...
Preprint
Full-text available
Background: Scleroderma (SSc) is a rare autoimmune disease characterized by vascular impairment and progressive fibrosis of the skin and other organs. Oncostatin M, a member of the IL-6 family, is elevated in SSc serum and was recognized as a significant player in various stages of fibrosis. The goal of this study was to assess the contribution of...
Preprint
Full-text available
Background Aldehyde dehydrogenase 1 (RALDH1)-producing dermal dendritic cells (DCs), a conventional DC subset regulating skin fibrosis, are decreased in the involved skin of patients with systemic sclerosis (SSc). In this study, we investigated the contribution of Fli1 deficiency, a potential predisposing factor of SSc, to the phenotypical alterati...
Article
Full-text available
Systemic sclerosis is an autoimmune disease characterized by fibrosis of skin and internal organs, vasculopathy, and dysregulation of immune system. A diagnostically important feature of immunological abnormalities in systemic sclerosis is the presence of circulating antinuclear antibodies, which may be detected in 90–95% of patients with either of...
Article
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Chronic inflammation is the underlying pathological condition that results in fibrotic diseases. More recently, many forms of cancer have also been linked to chronic tissue inflammation. While stromal immune cells and myofibroblasts have been recognized as major contributors of cytokines and growth factors that foster the formation of fibrotic tiss...
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Objective: Systemic sclerosis (SSc) is a clinically heterogeneous disease characterized by increased collagen accumulation and skin stiffness. Our previous work demonstrated that TGF-β induces extracellular matrix (ECM) modifications through lysyl oxidase-like 4 (LOXL4), a collagen cross-linking enzyme, in bioengineered human skin equivalents (hSE...
Article
Intravenous cyclophosphamide pulse, a standard treatment for systemic sclerosis (SSc)-related interstitial lung disease, elicits a disease-modifying effect on SSc vasculopathy, such as fostering microvascular de-remodeling. To investigate the molecular mechanism by which cyclophosphamide mitigates SSc vasculopathy, we employed endothelial cell–spec...
Article
Oncostain M, a member of the IL-6 family of cytokines, is produced by immune cells in response to infections and tissue injury. OSM has a broad, often context-dependent effect on various cellular processes including differentiation, hematopoiesis, cell proliferation, and cell survival. OSM signaling is initiated by binding to type I (LIFRβ/gp130) o...
Article
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Background Friend leukemia virus integration 1 (Fli1) deficiency, a predisposing factor of systemic sclerosis (SSc), induces SSc-like phenotypes in various cell types. A recent study demonstrated the transdifferentiation of T helper type 2 cell (Th2)-like regulatory T cells (Tregs) in SSc lesional skin through interleukin (IL)-33 produced by fibrob...
Article
Endothelial cell (EC) dysfunction has been associated with inflammatory and autoimmune diseases; however, the factors contributing to this dysfunction have not been fully explored. Because activation of TLRs has been implicated in autoimmune diseases, the goal of this study was to determine the effects of TLR ligands on EC function. Human dermal mi...
Chapter
Fibrogenesis is a multistage pathological process leading to scarring of virtually any organ. Fibrosis is characterized by disruption of normal tissue architecture and its replacement with stiff collagen-rich connective tissue. The process results in progressive functional impairment, culminating in organ failure. Fibrosis is the hallmark of sclero...
Article
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Systemic sclerosis (scleroderma, SSc) is a devastating fibrotic disease with few treatment options. Fumaric acid esters, including dimethyl fumarate (DMF, Tecfidera®) have shown therapeutic effects in several disease models, prompting us to determine whether DMF is effective as a treatment for SSc dermal fibrosis. We found that DMF blocks the pro-f...
Article
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Systemic sclerosis (SSc) is a complex disease characterized by early microvascular abnormalities, immune dysregulation and chronic inflammation, and subsequent fibrosis of the skin and internal organs. Excessive fibrosis, distinguishing hallmark of SSc, is the end result of a complex series of interlinked vascular injury and immune activation, and...
Article
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Background Systemic sclerosis (SSc) is characterized by fibrosis of the skin and internal organs. Although the involvement of connective tissue growth factor (CTGF/CCN2) has been well-documented in SSc fibrosis, the therapeutic potential of targeting CTGF in SSc has not been fully investigated. Our aim was to examine the therapeutic potential of CT...
Conference Paper
Background Oncostatin-M (OSM) and interleukin-6 (IL-6) are members of the IL-6 superfamily and signal via glycoprotein 130 (gp130). OSM signals with either the type I receptor complex, gp130/ Leukemia Inhibitory Factor Receptor (LIFR), or the type II receptor complex, gp130/OSM receptor (OSMR), whilst IL-6 signals via gp130 with the IL-6 receptor (...
Article
Full-text available
Systemic sclerosis (SSc), or scleroderma, is a multisystem autoimmune disorder characterized by vasculopathy and fibrosis in the skin and internal organs, most frequently in the esophagus and lungs. Hitherto, studies on SSc pathogenesis centered on immune cells, vascular cells, and fibroblasts. Although dysregulated keratinocytes in SSc have been r...
Article
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Systemic sclerosis (SSc) is a multi-organ fibrotic disease with few treatment options. Activated fibroblasts are the key effector cells in SSc responsible for the excessive production of collagen and the development of fibrosis. PDGF, a potent mitogen for cells of mesenchymal origin, has been implicated in the activation of SSc fibroblasts. Our aim...
Article
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Endothelial cell (EC) activation underlies many vascular diseases, including pulmonary arterial hypertension (PAH). Several members of the E-twenty six (ETS) family of transcription factors are important regulators of the gene network governing endothelial homeostasis, and their aberrant expression is associated with pathological angiogenesis. The...
Article
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Background Monocytes/macrophages are activated in several autoimmune diseases, including systemic sclerosis (scleroderma; SSc), with increased expression of interferon (IFN)-regulatory genes and inflammatory cytokines, suggesting dysregulation of the innate immune response in autoimmunity. In this study, we investigated whether the lytic form of Ep...
Article
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Pulmonary arterial hypertension (PAH) is a fatal condition for which there is no cure. Dimethyl Fumarate (DMF) is an FDA approved anti-oxidative and anti-inflammatory agent with a favorable safety record. The goal of this study was to assess the effectiveness of DMF as a therapy for PAH using patient-derived cells and murine models. We show that DM...
Article
W artykule zostały zebrane i opisane źródła ikonograficzne do dziejów herbu miasta Lublina z XV–XVIII w. przechowywane w zasobie Archiwum Państwowego w Lublinie. Wizerunki tego herbu podzielono na trzy grupy w zależności od rodzaju źródła i miejsca występowania znaku. Należą do nich: wyobrażenia na pieczęciach miasta, superekslibrisy na oprawach ks...
Article
Systemic sclerosis (SSc) is characterized by autoimmunity, small-vessel vasculopathy, and fibrosis causing damage in multiple organ systems. Pulmonary arterial hypertension (PAH) is a serious and often fatal complication of SSc, occurring in patients with the limited (lcSSc) and diffuse (dcSSc) forms of the disease and affecting 8% to 15% of patien...
Article
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Systemic sclerosis (SSc) is a multisystem inflammatory and vascular disease resulting in extensive tissue fibrosis. Glycyrrhizin, clinically used for chronic hepatic diseases and itching dermatitis, modulates the pathological processes of inflammation, vasculopathy, and fibrosis in human diseases and their animal models. Therefore, we investigated...
Data
Scatter plot of mean collagen expression vs. tumor purity estimates derived using the ABSOLUTE algorithm highlighting a moderate negative correlation (Pearson r = -0.32, p-value < 0.0001). (TIFF)
Data
Quantitative PCR expression for genes among top hits of collagen-based nearest neighbor analysis using fibroblasts isolated from OSCC specimens (RF), their adjacent epithelium (AE), CAL27 and HSC-3 cells. Fibroblast to cancer expression for each gene was calculated by averaging RF and AE, and CAL27 and HSC-3 values, respectively, normalizing the fo...
Article
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Carcinoma associated fibroblasts (CAFs) form the main constituents of tumor stroma and play an important role in tumor growth and invasion. The presence of CAFs is a strong predictor of poor prognosis of head and neck squamous cell carcinoma. Despite significant progress in determining the role of CAFs in tumor progression, the mechanisms contribut...
Data
Collagen-based nearest neighbor analysis results in OSCC. Genes are ranked in decreasing order of their Pearson correlation with respect to the mean expression of COL1A1, COL1A2 and COL3A1. FDRs indicate permutation-based significance estimates after multiple testing correction. The Gene_ID field represents both official HGNC gene symbols and Entre...
Data
Immunostaining highlighting localization of alpha smooth muscle actin (αSMA) in adjacent normal oral epithelium (AE), hyperplasia, ulcer, and OSCC tongue specimens. (TIFF)
Data
Pairwise gene expression Pearson correlation of the top 50 hits from collagen NN analysis within (A.) tumor and (B.) control TCGA OSCC samples. AE: Adjacent normal epithelium. (TIFF)
Data
Immunostaining highlighting localization of podoplanin in adjacent normal oral epithelium (AE), hyperplasia, ulcer, and OSCC tongue specimens. (TIFF)
Data
Gene-set enrichment analysis (GSEA) result table highlighting gene-sets positively enriched with respect to average collagen expression in OSCC. TCGA OSCC data was queried against canonical pathway genesets (c2.cp.v5.0) derived from the molecular signature database (MSigDb) using average collagen expression as a continuous ranking variable. (XLSX)
Conference Paper
Introduction Pulmonary arterial hypertension (PAH) is a serious, progressive and fatal complication of systemic sclerosis (SSc). Oxidative stress and chronic inflammation have been shown to play important roles in pathogenesis of PAH. Dimethyl Fumarate (DMF) (Tecfidera®) is an anti-oxidative and anti-inflammatory agent approved by the FDA for treat...
Article
Full-text available
HLA-B*35 is associated with increased risk of developing pulmonary hypertension in SSc patients. We previously reported that HLA-B*35 induces endothelial cell dysfunction via activation of ER stress/UPR and upregulation of the inflammatory response. Because PBMCs from lcSSc-PAH patients are also characterized by activation of ER stress/UPR and infl...
Article
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Objectives: Radiation-induced fibrosis is a common complication for patients following head and neck cancer treatment. This study presents a novel minimally invasive protocol for molecular study of fibrosis in the stromal tissues. Methods: Subjects with radiation-induced fibrosis in the head and neck who were at least 6 months post treatment rec...
Article
Members of the ETS family of transcription factors are involved in several developmental processes including endothelial cell specification and blood vessel formation, but their exact roles remain unclear. The family member Erg is highly expressed in endothelial cells as compared to other developing cell types including chondrocytes, hematopoietic...
Article
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Systemic sclerosis is a complex autoimmune disease characterized by a chronic and frequently progressive course and by extensive patient-to-patient variability. Like other autoimmune diseases, systemic sclerosis occurs more frequently in women, with a peak of onset in the fifth decade of life. The exact cause of systemic sclerosis remains elusive b...
Article
Objectives: It is generally accepted that blockade of endothelin receptors has potential beneficial effects on vasculopathy associated with systemic sclerosis (SSc). The aim of this study was to clarify the molecular mechanism underlying these effects using endothelial cell-specific Fli1 knockout (Fli1 ECKO) mice, an animal model of SSc vasculopath...
Article
Full-text available
Systemic sclerosis (SSc) is manifested by fibrosis, vasculopathy and immune dysregulation. So far, a unifying hypothesis underpinning these pathological events remains unknown. Given that SSc is a multifactorial disease caused by both genetic and environmental factors, we focus on the two transcription factors, which modulate the fibrotic reaction...
Article
Objective Fli-1, a potential predisposing factor for systemic sclerosis (SSc), is constitutively down-regulated in the lesional skin of patients with SSc by an epigenetic mechanism. To investigate the impact of Fli-1 deficiency on the induction of an SSc phenotype in various cell types, we generated bleomycin-induced skin fibrosis in Fli-1+/− mice...
Article
Full-text available
MMP-12, a macrophage-secreted elastase, is elevated in fibrotic diseases, including systemic sclerosis (SSc) and correlates with vasculopathy and fibrosis. The goal of this study was to investigate the role of MMP-12 in cardiac and cutaneous fibrosis induced by angiotensin II infusion. Ang II-induced heart and skin fibrosis was accompanied by a mar...
Article
Prolonged perturbation of the endoplasmic reticulum (ER) leads to ER stress and unfolded protein response (UPR) and contributes to the pathogenesis of various chronic disorders. This review focuses on the role of ER stress and UPR in endothelial cells and the relevance of these processes to vascular diseases. Chronic activation of ER stress and UPR...