Severe fibrosis and increased expression of fibrogenic cytokines in the gastric wall of systemic sclerosis patients

Manetti, Mirko; Neumann, Elena; Milia, Anna Franca; Tarner, Ingo H.; Bechi, Paolo; Matucci‐Cerinic, Marco; Ibba‐Manneschi, Lidia; Müller‐Ladner, Ulf

doi:10.1002/art.22940

Cited by 71 publications

(58 citation statements)

References 11 publications

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“…In summary the increase of fibrosis and the disturbed regulation of microcirculation as well as humoral and cellular changes is most likely the underlying cause for the impairment of the GIT in patients with systemic sclerosis [3].…”

Section: Discussionmentioning

confidence: 98%

“…The pathophysiology of SSc, especially of the GIT, is known only to a limited extent. This idea is not only based on clinical experience but on the only slowly increasing knowledge of pathways leading to increased fibrosis, altered regulation of microcirculation as well as of humoral and cellular changes similar to the alterations observed in SSc skin [2,3]. Clinically, SSc can present as diffuse (skin thickening proximal of the elbow and knee) and limited (skin thickening restricted to areas distal of elbow and knee) disease.…”

Section: Introductionmentioning

confidence: 99%

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Profile of gastrointestinal involvement in patients with systemic sclerosis

et al. 2011

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Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Of the numerous organ manifestations, involvement of the upper and lower gastrointestinal tract (GIT) appears to be the most frequent with regard to the clinical symptoms. However, as the frequency and clinical relevance of GI involvement in patients with SSc are not known in detail, the German network of the systemic sclerosis (DNSS) has developed a detailed questionnaire to evaluate the extent and profile of gastrointestinal involvement in SSc patients. The multi-symptom questionnaire was used at baseline and after 1 year in registered patients of the DNSS. In addition, the results were compared with gastrointestinal disorders in patients with SSc and other rheumatic diseases, as well as with the medical history of the patients. In total, 90 patients were included in the study. The results of the study show that in reality, a much higher (nearly all) percentage of (98,9%) patients than expected suffer from GI-symptoms, regardless of the stage of their disease. Of these, meteorism (87,8%) was the most common followed by coughing/sore voice (77,8%), heartburn (daytime 68,9%, nighttime 53,3%), diarrhea (67,8%), stomach ache (68,9%) and nausea (61,1%). Although SSc patients were treated according to the respective recommendations, only limited improvements with regard to GI-symptoms could be achieved after 1 year of follow-up. In addition, the study revealed that the multi-symptom questionnaire is a useful tool to contribute to identify the gastrointestinal sequelae in systemic sclerosis. Methods: The multi-symptom questionnaire was used at baseline and after one year in registered patients of the DNSS. In addition the results were compared with gastrointestinal disorders in patients with SSc and other rheumatic diseases, as well as with the medical history of the patients. In total, 90 patients were included in the study. Results: The results of the study show that in reality a much higher (nearly all) percentage of (98,9%) patients than expected suffer from GI-symptoms, regardless of the stage of their disease. Of these, meteorism (87,8%) was the most common followed by coughing/ sore voice (77,8%), heartburn (daytime 68,9%, nighttime 53,3%), diarrhea (67,8%), stomach ache (68,9%) and nausea (61,1%). Conclusions: Although SSc patients were treated according to the respective recommendations, only limited improvements with regard to GI-symptoms could be achieved after one year of follow up. In addition, the study revealed that the multi-symptom questionnaire is a useful tool to contribute to identify the gastrointestinal sequelae in systemic sclerosis. Methods:The multi-symptom questionnaire was used at baseline and after one year in registered patients of the DNSS. In addition the results were compared with gastrointestinal disorders in patients with SSc and other rheumatic diseases, as well as with the medical history of the patients. In total, 90 patients were included in the study. Results:The results of the study show tha...

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Profile of gastrointestinal involvement in patients with systemic sclerosis

et al. 2011

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“…It is noteworthy that the tendency for development of fibrosis in multiple organs can be an individual trait, as illustrated by gastric fibrosis in systemic sclerosis patients. 48 In these cases, at least a common pathogenesis is very likely.…”

Section: Characterization and Origin Of A Myofibroblastmentioning

confidence: 99%

Stromal myofibroblasts are drivers of invasive cancer growth

Wever¹,

Demetter²,

Mareel³

et al. 2008

Intl Journal of Cancer

623

601

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Tissue integrity is maintained by the stroma in physiology. In cancer, however, tissue invasion is driven by the stroma. Myofibroblasts and cancer-associated fibroblasts are important components of the tumor stroma. The origin of myofibroblasts remains controversial, although fibroblasts and bone marrow-derived precursors are considered to be the main progenitor cells. Myofibroblast reactions also occur in fibrosis. Therefore, we wonder whether nontumorous myofibroblasts have different characteristics and different origins as compared to tumor-associated myofibroblasts. The mutual interaction between cancer cells and myofibroblasts is dependent on multiple invasive growth-promoting factors, through direct cell-cell contacts and paracrine signals. Since fibrosis is a major side effect of radiotherapy, we address the question how the main methods of cancer management, including chemotherapy, hormonotherapy and surgery affect myofibroblasts and by inference the surrogate endpoints invasion and metastasis.

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“…These small vessel are vulnerable to mechanical irritation and contribute to anemia in these patients. In addition, vasoreactive molecules such as endothelin can also be found in full-thickness surgical samples (58), accompanied by a generalised fibrosis in the intestinal gastric wall, perivascular and around proliferating smooth muscle cells (59).…”

Section: Gastrointestinal Tractmentioning

confidence: 99%

Mechanisms of vascular damage in systemic sclerosis

et al. 2009

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Although being classified as autoimmune connective tissue disease, dominant components of the pathophysiology of systemic sclerosis (SSc) consists of mechanisms of vascular damage, which can occur early in the course of the disease. Amongst them are abnormal vasoreactivity, hypoxia, insufficient neoangiogenesis and direct damage of vascular and perivascular cells. They result in a decreased capillary blood flow, and subsequently in clinically overt symptoms such as Raynaud's syndrome and fingertip ulcers. In addition, in active disease vascular pathology can affect various other organs, predominantly the lung, the kidney, the heart but also the gastrointestinal tract. Vascular pathology contributes also significantly to overall morbidity and mortality in SSc patients and reduces life expectancy by at least a decade. Fortunately, molecular biology has revealed a number of underlying pathways on the cellular and subcellular levels, including key factors of the aberrant function of (peri)vascular cells and autoimmune effector cells, the dysregulation of vasoconstrictive molecules and their receptors, the upregulation of intracellular signaling kinases and the altered balance of hypoxia-induced vascular growth factors. This increasing knowledge of vascular pathology in SSc has also resulted in novel therapeutic approaches ranging from endothelin antagonists to application of progenitor cells to counteract this aberrant vascular pathology and to support the repair of the dysfunctional vasculature.

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Severe fibrosis and increased expression of fibrogenic cytokines in the gastric wall of systemic sclerosis patients

Cited by 71 publications

References 11 publications

Profile of gastrointestinal involvement in patients with systemic sclerosis

Profile of gastrointestinal involvement in patients with systemic sclerosis

Stromal myofibroblasts are drivers of invasive cancer growth

Mechanisms of vascular damage in systemic sclerosis

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