Biomarkers of skin and lung fibrosis in systemic sclerosis

Kaliterna, Dušanka Martinović; Petrić, Marin

doi:10.1080/1744666x.2020.1670062

Cited by 15 publications

(10 citation statements)

References 99 publications

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“…ROS cause chemical modifications in some lipids, proteins, and nucleic acids [ 250 ], which generate new epitopes that induce strong autoimmune responses. This is what has been shown in SSc, with ROS-associated changes in gene expression pattern and the stimulated release of IL-6, IL-8, and IL17 among others [ 251 , 252 ]. In this respect, diverse therapeutic strategies to interfere with ILs’ expression and/or their release have been successfully addressed with drugs such as the phosphodiesterase type 5 inhibitor sildenafil [ 253 ], the natural flavonoid kaempferol [ 254 ], EGCG [ 255 ], and the anti-IL-6 receptor antibody tocilizumab [ 256 ], among other treatments [ 257 ].…”

Section: Redox and Oxidative Stress In Genetic Diseases Of Connectsupporting

confidence: 71%

Reactive Oxygen Species and Oxidative Stress in the Pathogenesis and Progression of Genetic Diseases of the Connective Tissue

2020

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Connective tissue is known to provide structural and functional “glue” properties to other tissues. It contains cellular and molecular components that are arranged in several dynamic organizations. Connective tissue is the focus of numerous genetic and nongenetic diseases. Genetic diseases of the connective tissue are minority or rare, but no less important than the nongenetic diseases. Here we review the impact of reactive oxygen species (ROS) and oxidative stress on the onset and/or progression of diseases that directly affect connective tissue and have a genetic origin. It is important to consider that ROS and oxidative stress are not synonymous, although they are often closely linked. In a normal range, ROS have a relevant physiological role, whose levels result from a fine balance between ROS producers and ROS scavenge enzymatic systems. However, pathology arises or worsens when such balance is lost, like when ROS production is abnormally and constantly high and/or when ROS scavenge (enzymatic) systems are impaired. These concepts apply to numerous diseases, and connective tissue is no exception. We have organized this review around the two basic structural molecular components of connective tissue: The ground substance and fibers (collagen and elastic fibers).

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Section: Redox and Oxidative Stress In Genetic Diseases Of Connectsupporting

confidence: 71%

Reactive Oxygen Species and Oxidative Stress in the Pathogenesis and Progression of Genetic Diseases of the Connective Tissue

2020

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“…Since TGF‐β potently induces ECM protein synthesis, which is broadly responsible for fibrosis of many human organs including lung and kidney and cutaneous scarring, 9,37,38,40,41,46,58,59 we proposed that eCRT might exploit TGF‐β for ECM induction. To test this hypothesis, both eCRT‐treated HFFs and human adult dermal fibroblasts (HDFs) were analyzed for ECM mRNA and protein expression in the presence or absence of the specific serine‐threonine kinase inhibitor of TβRI signaling, SD208.…”

Section: Resultsmentioning

confidence: 99%

Calreticulin exploits TGF‐β for extracellular matrix induction engineering a tissue regenerative process

et al. 2020

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Topical application of extracellular calreticulin (eCRT), an ER chaperone protein, in animal models enhances wound healing and induces tissue regeneration evidenced by epidermal appendage neogenesis and lack of scarring. In addition to chemoattraction of cells critical to the wound healing process, eCRT induces abundant neo-dermal extracellular matrix (ECM) formation by 3 days post-wounding. The purpose of this study was to determine the mechanisms involved in eCRT induction of ECM. In vitro, eCRT strongly induces collagen I, fibronectin, elastin, α-smooth muscle actin in human adult dermal (HDFs) and neonatal fibroblasts (HFFs) mainly via TGF-β canonical signaling and Smad2/3 activation; RAP, an inhibitor of LRP1 blocked eCRT ECM induction. Conversely, eCRT induction of α5 and β1 integrins was not mediated by TGF-β signaling nor inhibited by RAP. Whereas eCRT strongly induces ECM and integrin α5 proteins in K41 wild-type mouse embryo fibroblasts (MEFs), CRT null MEFs were unresponsive. The data show that eCRT induces the synthesis and release of TGF-β3 first via LRP1 or other receptor signaling and later induces ECM proteins via LRP1 signaling subsequently initiating TGF-β receptor signaling for intracellular CRT (iCRT)-dependent induction of TGF-β1 and ECM proteins. In addition, TGF-β1 induces 2-3-fold higher level of ECM proteins than eCRT. Whereas eCRT and iCRT converge for ECM induction, we propose that eCRT attenuates TGF-β-mediated fibrosis/scarring to achieve tissue regeneration.

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“…That is to say, the last two decades have proven HRCT to be clinically useful in the detection of ILD; therefore, it has consequently assumed a pivotal role by default. Indeed, several studies have addressed the potential of lung HRCT as a screening tool for ILD in SSc [16,[35][36][37][38][39][40][41][42][43][44][45]. However, radiation exposure remains a question to be taken into consideration.…”

Section: The Role Of Hrtc In Ssc-ildmentioning

confidence: 99%

High-Resolution Computed Tomography: Lights and Shadows in Improving Care for SSc-ILD Patients

et al. 2021

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The diagnosis and classification of systemic sclerosis-associated interstitial lung disease (SSc-ILD) is essential to improve the prognosis of systemic sclerosis (SSc) patients. The risk-stratification of disease severity and follow-up requires a multidisciplinary approach, integrating high-resolution computed tomography (HRTC) of the lung, pulmonary function tests (PFT), along with clinical and symptomatic evaluations. The use of HRCT in detecting SSc-ILD is not so much based on a definitive validation, but rather reflects the widespread clinician recognition of dissatisfaction with other modalities. However, due to the heterogeneity of SSc-ILD and the potential absence of symptoms in early or mild disease, it is prudent to consider as many parameters as possible in the assessment and monitoring of newly diagnosed patients. An early diagnosis meets the primary goal, i.e., the prevention of disease progression. The current first line treatment regimens are mainly centered on immunosuppressive therapy. This review assesses the role HRCT plays in optimizing care and improving clinical outcomes in SSc-ILD patients.

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Biomarkers of skin and lung fibrosis in systemic sclerosis

Cited by 15 publications

References 99 publications

Reactive Oxygen Species and Oxidative Stress in the Pathogenesis and Progression of Genetic Diseases of the Connective Tissue

Reactive Oxygen Species and Oxidative Stress in the Pathogenesis and Progression of Genetic Diseases of the Connective Tissue

Calreticulin exploits TGF‐β for extracellular matrix induction engineering a tissue regenerative process

High-Resolution Computed Tomography: Lights and Shadows in Improving Care for SSc-ILD Patients

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