Fibrosis — A Common Pathway to Organ Injury and Failure

Urban, Maria Letizia; Manenti, Lucio; Vaglio, Augusto

doi:10.1056/nejmc1504848

Cited by 180 publications

(70 citation statements)

References 9 publications

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“…Secondly, RDN significantly reduces pro-fibrosis factors and inflammation cytokines production. Abundant experimental evidence supports the notion that TGF-β1 plays an important role in the pathogenesis of fibrosis 1 34 . Simultaneously, TGF-β1 can upregulate mRNA level of MMP2 in cardiac fibroblasts, and the elevated protein expression of MMP2 could promote the activation of fibroblasts 42 , further increasing the collagen synthesis.…”

Section: Discussionmentioning

confidence: 84%

“…Fibrosis is a common pathway to organ injury and failure 1 . A 3% increase in the CVF of fibrous tissue is associated with a 50% increase in the risk of adverse cardiovascular events 20 .…”

Section: Discussionmentioning

confidence: 99%

“…Cardiac and renal fibrosis is the result of various cardiovascular injuries. Vice versa, cardio-renal fibrosis promotes heart and kidney disease progression 1 . Both left atrium (LA) enlargement and LA fibrosis play key roles in developing and sustaining atrial fibrillation 2 3 .…”

mentioning

confidence: 99%

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Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy

Liu

Zhang

Wang

et al. 2015

Sci Rep

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Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced cardiomyopathy rats were randomized to RDN (n = 15) and Sham group (n = 16). Compared with Control group, ejection fraction was decreased, diastolic interventricular septal thickness and left atrial dimension were increased in ISO-induced cardiomyopathy group at 5 week. After 10 weeks, cardio-renal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the pro-fibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-α), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin II type-1 receptor (AT1R) axis was downregulated. Meanwhile, angiotensin-converting enzyme 2 (ACE2)/angiotensin-1-7 (Ang-(1-7))/mas receptor (Mas-R) axis was upregulated. RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis.

show abstract

Section: Discussionmentioning

confidence: 84%

“…Fibrosis is a common pathway to organ injury and failure 1 . A 3% increase in the CVF of fibrous tissue is associated with a 50% increase in the risk of adverse cardiovascular events 20 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy

Liu

Zhang

Wang

et al. 2015

Sci Rep

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“…It is a secreted protein that performs many cellular functions including the control of cell growth, proliferation, differentiation, and apoptosis [138]. TGF-β is also a potent stimulator of the synthesis of extracellular matrix proteins and plays a prominent role in the development of tissue fibrosis [139]. Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine that is produced by multiple immune cell types and has many roles including mediating the activation and survival of eosinophils [140, 141].…”

Section: Cytokines Chemokines and Other Moleculesmentioning

confidence: 99%

The Immunologic Mechanisms of Eosinophilic Esophagitis

Hill

Spergel

2016

Curr Allergy Asthma Rep

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Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disease that is triggered by food and/or environmental allergens and is characterized by a clinical and pathologic phenotype of progressive esophageal dysfunction due to tissue inflammation and fibrosis. EoE is suspected in patients with painful swallowing, among other symptoms, and is diagnosed by the presence of 15 or more eosinophils per high-power field in one or more of at least four esophageal biopsy specimens. The prevalence of EoE is increasing and has now reached rates similar to those of other chronic gastrointestinal disorders such as Crohn’s disease. In recent years, our understanding of the immunologic mechanisms underlying this condition has grown considerably. Thanks to new genetic, molecular, cellular, animal, and translational studies, we can now postulate a detailed pathway by which exposure to allergens results in a complex and coordinated type 2 inflammatory cascade that, if not intervened upon, can result in pain on swallowing, esophageal strictures, and food impaction. Here, we review the most recent research in this field to synthesize and summarize our current understanding of this complex and important disease.

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“…TGF-β controls cell growth, proliferation, differentiation, and apoptosis as well as stimulation of ex-tracellular ma-trix proteins resulting in the development of tissue fibrosis [17]. Some studies have shown that polymorphisms in the promoter of TGF-β are associated with susceptibility to EOE [18][19][20][21][22]. The de-crease in the level of peripheral Tregs has been reported in patients with chronic urticaria [23].…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of Interleukin-10 and Tumor Growth Factor-β1 in Children With Eosinophilic Gastrointestinal Disorders Compared to Control Groups

et al. 2019

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Background: Eosinophilic Gastrointestinal Disorders (EGID) are a heterogeneous group of gastrointestinal disorders, associated with an increase of the eosinophils in the gastrointestinal mucosal tissue. Regulatory T cells (Tregs), as a subset of T cells, have a proven prominent role in immunopathology and protection against allergic diseases. Also, they appear to play a role in EGID pathogenesis. In the present study, serum levels of Tumor Growth Factor (TGF)-β and interleukin (IL)-10 were measured in patients with EGID compared to patients with Gastroesophageal Reflux Disease (GERD) and healthy subjects. Materials and Methods: A total of 34 patients with EGID, 23 with GERD, and 25 healthy controls were included in the study. The diagnoses of EGID and GERD were made based on the patients' clinical symptoms, endoscopic findings, and biopsy confirmation. A questionnaire of demographic information, allergy history, as well as endoscopic-pathological and skin prick test results were completed and performed. The serum levels of TGF-β and IL-10 were measured using the ELISA method. Results: Family history of allergic disorders in patients with EGID or GERD was significantly high compared to healthy controls (P=0.010, P=0.005, respectively). There was a statistically significant increase in serum levels of TGF-β1 (P=0.025), but no significant difference was observed in serum level of IL-10 among three groups. However, the serum level of IL-10 was significantly high in a subgroup of patients with upper gastrointestinal eosinophilic involvement compared to the healthy controls (P=0.018). Conclusion: Significant increase in the serum level of IL-10 and TGF-β might be due to the Tregs dysfunction in EGID patients. Further studies should determine the role of Tregs in the pathogenesis of EGID.

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Fibrosis — A Common Pathway to Organ Injury and Failure

Cited by 180 publications

References 9 publications

Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy

Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy

The Immunologic Mechanisms of Eosinophilic Esophagitis

Serum Levels of Interleukin-10 and Tumor Growth Factor-β1 in Children With Eosinophilic Gastrointestinal Disorders Compared to Control Groups

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