An Evaluation of SPARC Protein as a Serum Biomarker of Chronic Rhinosinusitis

Asmar, Marc‐Henri; Gaudreau, Annie; Maniakas, Anastasios; Endam, Léandra Mfuna; Desrosiers, Martin

doi:10.1177/0194599818801888

Cited by 5 publications

(4 citation statements)

References 32 publications

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“…Its levels are elevated in tissues with high cell turnover, in embryonic development and in response to injury but it is reduced in normal adult tissues suggesting its key role in tissue regeneration and repair 37,38 . In the lung, SPARC has been described to be involved in cancer development, in chronic airway diseases and pulmonary fibrosis [39][40][41][42][43] where it controls tissue remodeling, cell proliferation and migration. In lung fibrosis SPARC has been shown suppress apoptosis of IPF lung fibroblasts 44 and being a down-stream effector of the profibrotic cytokine TGF-β 43,45 .…”

Section: Discussionmentioning

confidence: 99%

Paracrine SPARC signaling dysregulates alveolar epithelial barrier integrity and function in lung fibrosis

et al. 2020

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Idiopathic pulmonary fibrosis (IPF) is a chronic scarring disease in which aging, environmental exposure(s) and genetic susceptibility have been implicated in disease pathogenesis, however, the causes and mechanisms of the progressive fibrotic cascade are still poorly understood. As epithelial-mesenchymal interactions are essential for normal wound healing, through human 2D and 3D in vitro studies, we tested the hypothesis that IPF fibroblasts (IPFFs) dysregulate alveolar epithelial homeostasis. Conditioned media from IPFFs exaggerated the wound-healing response of primary human Type II alveolar epithelial cells (AECs). Furthermore, AECs co-cultured with IPFFs exhibited irregular epithelialization compared with those co-cultured with control fibroblasts (NHLFs) or AECs alone, suggesting that epithelial homeostasis is dysregulated in IPF as a consequence of the abnormal secretory phenotype of IPFFs. Secretome analysis of IPFF conditioned media and functional studies identified the matricellular protein, SPARC, as a key mediator in the epithelial-mesenchymal paracrine signaling, with increased secretion of SPARC by IPFFs promoting persistent activation of alveolar epithelium via an integrin/focal adhesion/cellular-junction axis resulting in disruption of epithelial barrier integrity and increased macromolecular permeability. These findings suggest that in IPF fibroblast paracrine signaling promotes persistent alveolar epithelial activation, so preventing normal epithelial repair responses and restoration of tissue homeostasis. Furthermore, they identify SPARC-mediated paracrine signaling as a potential therapeutic target to promote the restoration of lung epithelial homoestasis in IPF patients.

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Section: Discussionmentioning

confidence: 99%

Paracrine SPARC signaling dysregulates alveolar epithelial barrier integrity and function in lung fibrosis

et al. 2020

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“…In addition, basophils circulating in blood are transferred to tissues where they are transformed into mast cells (Naclerio et al, 2017). In a previous study that investigated the serum secreted protein acidic and cysteine-rich (SPARC) value in 26 patients with CRSwNP before and after endoscopic sinus surgery (ESS), the postoperative serum SPARC value was decreased by 33%, but the authors noted that it was not possible to use SPARC to predict the course of the disease after ESS (Asmar et al, 2019). In another study, the authors sought an answer to the question of whether the serum periostin value could be used to determine the nasal polyp load in CRSwNP patients and found the level of this protein to be higher in CRSwNP patients compared to the CRSwoNP group.…”

Section: Discussionmentioning

confidence: 99%

A proinflammatory marker in chronic rhinosinusitis: serum calprotectin

Çandar

Baklacı

Kuzucu³

et al. 2020

Acta Biochim Pol

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Introduction: Studies have shown that calprotectin has a strong pro-inflammatory effect. Elevated calprotectin levels in the serum can be used as a strong clinical marker indicating the presence of inflammation. Objective: To investigate serum calprotectin levels in patients with chronic rhinosinusitis (CRS) and to determine the applicability of calprotectin as a potential molecular pro-inflammatory biomarker for CRS. Methods: The study consisted of three groups: chronic rhinosinusitis with polyps (CRSwNP group), chronic rhinosinusitis without polyps (CRSwoNP), and healthy control. CRS patients with polyps were further divided into two groups depending on the presence/absence of Samter’s triad. The Nose Obstruction Symptom Evaluation (NOSE) scale score and serum calprotectin value were evaluated in all participants. Results: The mean serum calprotectin value was 79.5±11.8 ng/ml for the CRSwNP group, 71.3±16 ng/ml for the CRSwoNP group, and 61.9±11.6 ng/ml for the control group (p<0.001). The Samter’s triad group had a significantly higher calprotectin value than the non-Samter’s triad group (p=0.03). There was a significant correlation between the NOSE scores and calprotectin levels (rho=0.734, p<0.001). Conclusion: Serum calprotectin values were correlated with the severity of symptoms in patients with CRS; thus, it seems to be a valuable pro-inflammatory biomarker for the diagnosis of the disease and determining its severity. Further studies with larger series are needed to evaluate the preoperative and postoperative serum calprotectin values in patients undergoing surgery.

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“… 10 11 12 In the lung, SPARC has been studied to be linked to cancer pathogenesis, pulmonary fibrosis, pulmonary vascular remodeling and chronic airway diseases. 11 13 14 15 Veith et al 14 revealed that SPARC was one of consistently downregulated genes by whole genome DNA microarray analysis in a reverse-remodeling model of pulmonary hypertension, and SPARC knockdown in adult mice by adeno-associated virus dramatically improved hemodynamic and pulmonary vascular remodeling. Chang et al 11 found SPARC down-regulation attenuated alpha smooth muscle actin (α-SMA) in idiopathic pulmonary fibrosis (IPF) fibroblasts.…”

Section: Introductionmentioning

confidence: 99%

Suppression of SPARC Ameliorates Ovalbumin-induced Airway Remodeling via TGFβ1/Smad2 in Chronic Asthma

Pan,

Zhang,

Zhang

et al. 2024

Allergy Asthma Immunol Res

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Purpose Airway remodeling is a critical feature of asthma. Secreted protein acidic and rich in cysteine (SPARC), which plays a cardinal role in regulating cell-matrix interactions, has been implicated in various fibrotic diseases. However, the effect of SPARC in asthma remains unknown. Methods We studied the expression of SPARC in human bronchial epithelial cells and serum of asthmatics as well as in the lung tissues of chronic asthma mice. The role of SPARC was examined by using a Lentivirus-mediated SPARC knockdown method in the ovalbumin (OVA)-induced asthma mice. The biological processes regulated by SPARC were identified using RNA sequencing. The function of SPARC in the remodeling process induced by transforming growth factor β1 (TGFβ1) was conducted by using SPARC small interfering RNA (siRNA) or recombinant human SPARC protein in 16HBE cells. Results We observed that SPARC was up-regulated in human bronchial epithelia of asthmatics and the asthmatic mice. The levels of serum SPARC in asthmatics were also elevated and negatively correlated with the forced expiratory volume in one second (FEV1) to forced vital capacity ratio (FVC) ( r = −0.485, P < 0.01) and FEV1 (%predicted) ( r = −0.425, P = 0.001). In the chronic asthmatic mice, Lentivirus-mediated SPARC knockdown significantly decreased airway remodeling and airway hyper-responsiveness. According to gene set enrichment analysis, negatively enriched pathways found in the OVA + short hairpin-SPARC group included ECM organization and collagen formation. In the lung function studies, knockdown of SPARC by siRNA reduced the expression of remodeling-associated biomarkers, cell migration, and contraction by blocking the TGFβ1/Smad2 pathway. Addition of human recombinant SPARC protein promoted the TGFβ1-induced remodeling process, cell migration, and contraction in 16HBE cells via the TGFβ1/Smad2 pathway. Conclusions Our studies provided evidence for the involvement of SPARC in the airway remodeling of asthma via the TGFβ1/Smad2 pathway.

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An Evaluation of SPARC Protein as a Serum Biomarker of Chronic Rhinosinusitis

Abstract: No sponsorships or competing interests have been disclosed for this article.

Cited by 5 publications

References 32 publications

Paracrine SPARC signaling dysregulates alveolar epithelial barrier integrity and function in lung fibrosis

Paracrine SPARC signaling dysregulates alveolar epithelial barrier integrity and function in lung fibrosis

A proinflammatory marker in chronic rhinosinusitis: serum calprotectin

Suppression of SPARC Ameliorates Ovalbumin-induced Airway Remodeling via TGFβ1/Smad2 in Chronic Asthma

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