Periostin In Tissues Research Articles

Periostin acts as an oncogene to promote laryngeal cancer progression by activating decorin.

Laryngeal carcinoma (LC) is the second most common malignancy of the head and neck worldwide, with increasing incidence every year. However, the mechanism of its development is not completely clear. Periostin (POSTN) has been reported to be involved in various aspects of tumorigenesis. To determine the influence of POSTN on LC tumorigenesis, we first examined the expression of POSTN in tissues from patients with LC through immunohistochemistry, western blot, and qRT-PCR. Besides, we demonstrated that POSTN promoted LC cell migration, invasion, and proliferation in vitro by CCK-8, colony formation, and Transwell assays, and tumor growth in vivo by immunohistochemistry. Furthermore, the interaction between POSTN and decorin (DCN) was further verified by bioinformatics analysis and immunoprecipitation (IP), finding that POSTN promoted the malignant progression of LC by targeting DCN. Our findings support the idea that the level of POSTN expression and accumulation in tumors correlated with the malignancy degree of LC, suggesting that POSTN may play a potential role in improving laryngeal cancer treatment strategies.

Mapping the Periostin splice isoforms in atopic dermatitis and an in vitro asthma model – A multi-platform analysis using mass spectrometry and RT-qPCR

Periostin is a matricellular protein known to be alternatively spliced to produce ten isoforms with a molecular weight of 78–91 kDa. Within the extracellular matrix, periostin attaches to cell surfaces to induce signaling via integrin-binding and actively participates in fibrillogenesis, orchestrating the arrangement of collagen in the extracellular environment. In atopic diseases such as atopic dermatitis (AD) and asthma, periostin is known to participate in driving the disease-causing type 2 inflammation. The periostin isoforms expressed in these diseases and the implication of the alternative splicing events are unknown. Here, we present two universal assays to map the expression of periostin isoforms at the mRNA (RT-qPCR) and protein (PRM-based mass spectrometry) levels. We use these assays to study the splicing profile of periostin in AD lesions as well as in in vitro models of AD and asthma. In these conditions, periostin displayed overexpression with isoforms 3 and 5 standing out as highly overexpressed. Notably, isoforms 9 and 10 exhibited a divergent pattern relative to the remaining isoforms. Isoforms 9 and 10 are often overlooked in periostin research and this paper presents the first evidence of their expression at the protein level. This underlines the necessity to include isoforms 9 and 10 in future research addressing periostin splice isoforms. The assays presented in this paper hold the potential to improve our insight into the splicing profile of periostin in tissues and diseases of interest. The application of these assays to AD lesions and in vitro models demonstrated their potential for identifying isoforms of particular significance, warranting a further in-depth investigation.

Periostin promotes EMT via inhibition of RIN1-mediated endocytosis of EGFR in gliomas

PurposeApproximately 1/3 of brain tumors are gliomas. Previous glioma-related studies have reported increased expression of periostin (POSTN) in these cancerous tissues, but the role and mechanism of POSTN in glioma development remain unclear.MethodsNanoscale liquid chromatography coupled with tandem mass spectrometry (nano LC–MS/MS) and RNA sequencing were used to identify differential protein and mRNA expression in clinical glioma samples. Quantitative real-time PCR (qRT–PCR) was used to measure the expression of POSTN in tissues and cells. The effects of POSTN on glioma cell migration and invasion were examined using wound healing, Transwell, and three-dimensional spheroid assays in vitro and a nude mouse xenograft model in vivo. The effects of POSTN on the stability, endocytosis, and degradation of EGFR were examined by immunoblotting and immunofluorescence staining. Truncation mutation analysis was performed to investigate direct interactions between POSTN and EGFR. Immunohistochemical staining was carried out to confirm the clinical significance of POSTN.ResultsOverexpression of POSTN induced epithelial-to-mesenchymal transition (EMT) in glioma cells in vivo and in vitro. Mechanistically, POSTN downregulation inhibited EGFR signaling by promoting EGFR endocytosis and degradation. In addition, POSTN was found to bind to EGFR and RIN1, inhibiting EGFR endocytosis and degradation and thus activating the PI3K-Akt signaling pathway.ConclusionThese findings indicate the mechanism by which the POSTN/EGFR/RIN1 axis inhibits EGFR endocytosis and degradation, resulting in glioma cell EMT through the PI3K-AKT signaling pathway. Targeting POSTN/EGFR/RIN1 interactions may guarantee beneficial outcomes of glioma treatment.

The diagnostic importance of periostin as a biomarker in chronic rhinosinusitis with nasal polyp.

PurposeThe current studies in the literature report that periostin contributes to the formation of nasal polyps and may be a molecular biomarker for chronic rhinosinusitis with nasal polyps (CRSwNP). This study aims to investigate the effect of periostin in determining polyp burden in CRSwNP patients and evaluate its impact on postoperative surgical results and its functionality as a biomarker.MethodsThe study included 26 patients who underwent endoscopic sinus surgery due to CRSwNP and 30 patients who were scheduled to undergo septoplasty due to isolated nasal septum deviation. We performed preoperative Lund–Mackay scoring and preoperative and postoperative SNOT-22 and Modified Lund–Kennedy scoring for the patients. Tissue and serum samples were collected from all patients in surgery and another serum sample was taken from CRSwNP patients at postoperative month 6.ResultsTissue eosinophil (p < 0.001), preoperative serum (p < 0.001), and tissue (p = 0.002) periostin were significantly higher in the CRSwNP group. We observed a statistically significant positive correlation between tissue eosinophil values and tissue periostin values in CRSwNP patients (p = 0.004). We found a statistically significant positive correlation between the tissue periostin values and postoperative SNOT-22 scores of the CRSwNP group patients (p = 0.005).ConclusionAccording to the results of our study, we think that periostin can be used as a biomarker in the prediction, determination of disease severity, and prognosis of CRSwNP. Comprehensive cohort studies with larger patient series are needed to provide more information on the role and effects of periostin in cases of CRSwNP undergoing surgical treatment.

Periostin is Oncogenic and Promotes EMT in Gliomas via Inhibition of RIN1-Mediated Endocytosis of EGFR

Background: About 1/3 of all brain tumors are gliomas. Previous glioma studies have reported increased expression of Periostin (POSTN) in these cancerous tissues, but its role and mechanism in gliomas development remain unknown. Methods: Nanoscale liquid chromatography coupled to tandem mass spectrometry (Nano LC-MS/MS) and RNA sequencing were used to identify differential protein and mRNA expression in glioma samples from the clinic. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of POSTN in tissues and cells. The effects of POSTN on glioma cell migration and invasion were examined using wound-healing, transwell, and three-dimensional spheroid assays in vitro, and a xenograft nude-mouse model in vivo. POSTN’s effect on the stability, endocytosis, and degradation of EGFR was examined by immunoblotting and immunofluorescence. Truncated mutation analysis was performed to interrogate any direct interactions between POSTN and EGFR. Immunohistochemical staining was carried out to confirm the clinical significance of POSTN. Findings: In this study, POSTN was upregulated in gliomas and was associated with poor prognosis. POSTN depletion inhibited glioma epithelial-to-mesenchymal transition (EMT) both in vitro and in vivo. Furthermore, POSTN downregulation dampened EGFR signaling via promotion of EGFR endocytosis and degradation. In addition, POSTN was found to bind to EGFR and RIN1, inhibiting EGFR endocytosis and degradation, thus promoting the activation of the PI3K-AKT signaling pathway. Interpretation: These findings indicate the POSTN/EGFR/RIN1 axis inhibits EGFR endocytosis and degradation. Targeting POSTN/EGFR/RIN1 interactions may prove beneficial the treatment of gliomas. Funding Information: This work was supported by grants from National Natural Science Foundation of China (81772682), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). Declaration of Interests: The authors have declared that no competing interest exists. Ethics Approval Statement: Our study protocol was approved by the Research Ethics Committee of Nanjing Medical University (Nanjing, Jiangsu, China).

The role of periostin in kidney diseases.

Chronic kidney disease (CKD) is a multi-symptomatic condition resulting from irreversible functional and structural damage to the kidneys. Therefore, finding a specific and sensitive marker to predict the development and progression of CKD is of great interest. Periostin is a matricellular protein involved in tissue remodeling and wound healing. It is highly expressed in various types of kidney diseases, especially in conditions associated with progressive renal fibrosis, while its expression in healthy kidneys is not significant. Numerous experimental and human adult studies indicate the role of periostin in the pathogenesis of various types of kidney disease, though the mechanism of action of periostin appears to be diverse and varies depending on the conditions. The article summarizes current knowledge on the possible roles of periostin in the pathogenesis of kidney injury and its position as a marker in various human renal pathologies. The studies performed so far indicate the potential of urinary and tissue periostin as a promising biomarker of CKD progression.

Effects of periostin on hepatocellular carcinoma cells invasion, metastasis and prognosis

Objective: To investigate the prognostic relationship between the expression levels of periostin (POSTN) in hepatocellular carcinoma (HCC) tissues as well as its effect in invasion and metastasis. Methods: The expression levels of POSTN in liver cancer tissues were detected with real-time quantitative PCR (QPCR) and immunohistochemistry (IHC). Kaplan-Meier method and Log-rank test were used to analyze the relationship between POSTN expression level and postoperative prognosis in patients with liver cancer. The expression of POSTN in hepatocellular carcinoma cells with different metastasis characteristics were detected in vitro and the overexpression of POSTN in low metastatic hepatocellular carcinoma cells was mediated through plasmid transfection techniques. The effects of POSTN on invasion and metastasis of hepatocellular carcinoma cells were determined by transwell migration and matrigel invasion assay. The comparative expression level of POSTN was analyzed by t-test. Results: The expression levels of POSTN in tissues from high to low was in the order of metastatic liver cancer tissues, non-metastatic liver cancer tissues and normal liver tissues (P = 0.006). The median survival time and 3-year survival rate in postoperative patients with hepatocellular carcinoma of high POSTN expression level were significantly lower than the low expression group (10.00 months, 44.44%; 59.00 months, 53.13%, P = 0.031 2). In in vitro testing, the expression of POSTN was highest in MHCC97H cells with high metastatic characteristics as compared with Huh7 and MHCC97L cells with low and medium metastatic characteristics. After overexpression of POSTN in MHCC97L cells, the migration and invasion capacity of MHCC97L cells was increased. Conclusion: POSTN is associated with pathological processes such as metastasis and invasion of liver cancer, which may promote the migration and invasion of liver cancer cells. It is expected to be an important prognostic biomarker of tumor recurrence and a therapeutic target for inhibiting the occurrence of metastasis in postoperative patients with hepatocellular carcinoma.

Expression and Significance of Periostin in Tissues and Serum in Oral Leukoplakia and Squamous Cell Carcinoma.

Objective: This study aims to investigate the expression changes of periostin (PN or OSF-2) in oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC), and analyze its significance in the development of OSCC. Study Design: The expression of periostin was detected from tissue specimens and serum obtained from normal mucosa, OLK and OSCC by immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative polymerase chain reaction. Results: Periostin was significantly overexpressed in OLK and OSCC, when compared with normal controls (p < 0.05). Furthermore, the overexpression of periostin was positively correlated with TNM stage, depth of invasion, and lymph node metastasis (p < 0.05). Conclusion: The overexpression of periostin may be involved in the carcinogenesis process of OLK, which may be used as a marker for detecting OLK. In addition, periostin serum levels can be used as a potential indicator of invasion and a prognosis target for OSCC.

Prospective assessment of serum periostin as a biomarker for diagnosis and monitoring of eosinophilic oesophagitis.

Periostin is highly expressed in eosinophilic oesophagitis (EoE), but has not been extensively studied as a non-invasive biomarker. To assess whether serum periostin distinguished EoE from controls at baseline, had utility for monitoring treatment response, or was associated with IL-13 levels. This was a sub-analysis of a prospective cohort study of adults undergoing out-patient upper endoscopy. Incident cases of EoE were diagnosed per consensus guidelines. Controls were subjects with either GERD or dysphagia without EoE. EoE patients were treated with swallowed/topical steroids and had repeat endoscopy/biopsy. Serum periostin levels for cases and controls were compared at baseline, and pre/post-treatment levels were compared for cases. Serum IL-13 and tissue expression of periostin were also assessed. A total of 61 incident EoE cases and 87 controls were analysed. Despite a marked increase in tissue periostin expression in cases, the median baseline serum periostin level was only slightly higher in cases than controls (22.1 ng/mL vs. 20.7; P = 0.04); there was no change in post-treatment levels. There was also no difference in serum periostin for cases by histologic response or atopic status. There was a strong trend towards higher serum IL-13 levels in cases in the highest periostin quartile (57.1 pg/mL vs. 2.6; P = 0.07). Serum periostin levels were similar in cases and controls, and there were no changes post-treatment. Given elevated IL-13 levels in the EoE patients with the highest periostin levels, future studies could explore periostin as a biomarker in EoE, perhaps in the setting of anti-IL-13 therapy.

Overexpression of periostin predicts poor prognosis in non-small cell lung cancer

The periostin protein, encoded by the POSTN gene, is a component of the extracellular matrix, which is expressed by fibroblasts and has been observed in a variety of human malignancies. The present study aimed to detect the expression of periostin in the tissues of non-small cell lung cancer (NSCLC) patients and benign lung tumors, and to correlate the results with the clinicopathological data of the subjects, in order to evaluate periostin as a potential prognostic marker. In total, 49 NSCLC patients and 6 benign lung tumors were included in this study. The protein level of periostin was detected in paired normal/paratumor/cancer tissues by a western blot analysis and the mRNA level in paired normal/cancer tissues was detected by quantitative polymerase chain reaction (qPCR). The results were then correlated with established biological and prognostic factors. Immunohistochemistry was used to confirm the location of periostin in the NSCLC tissues. Uni- and multivariate analyses were performed using Cox’s proportional hazards regression model. The protein level of periostin was elevated in the cancer tissue of the NSCLC patients compared with the normal (P=0.017) and paratumor (P=0.000) tissues. The expression level in the male patients was much higher than in the female patients at the protein (P=0.001) and mRNA (P=0.010) levels. The mRNA level in the non-adenocarcinoma (non-ADC) patients was much higher than in the adenocarcinoma (ADC) patients (P=0.029). Periostin was demonstrated higher expression at the protein level in the pseudotumors and tuberculosis patients than in the adjacent (P=0.016) and surrounding tissues (P=0.001). Immunostaining indicated that high levels of periostin were present in the mesenchymal areas, but not in the cancer cells themselves. The patients with tumors exhibiting high-level periostin expression showed a significantly shorter survival time (P=0.036, log-rank test). The 3-year survival rate was 81.5% for patients with low-level periostin expression (periostin-L; n=27) and 45.4% for patients with high-level periostin expression (periostin-H; n=22). Similarly, pathological node (pN) status was a significant prognostic marker in the univariate Cox survival analysis. Notably, periostin-H expression was also identified as an independent prognostic factor by the multivariate analysis (P=0.011). These results showed that the overexpression of periostin predicts a poor prognosis, therefore it may be regarded as a novel molecule in the progression and development of NSCLC. The results provide an additional target for the adjuvant treatment of NSCLC.

Periostin as a modulator of chronic cardiac remodeling after myocardial infarction

OBJECTIVE:After acute myocardial infarction, during the cardiac repair phase, periostin is released into the infarct and activates signaling pathways that are essential for the reparative process. However, the role of periostin in chronic cardiac remodeling after myocardial infarction remains to be elucidated. Therefore, the objective of this study was to investigate the relationship between tissue periostin and cardiac variables in the chronic cardiac remodeling induced by myocardial infarction.METHODS:Male Wistar rats were assigned to 2 groups: a simulated surgery group (SHAM; n = 8) and a myocardial infarction group (myocardial infarction; n = 13). After 3 months, morphological, functional and biochemical analyses were performed. The data are expressed as means±SD or medians (including the lower and upper quartiles).RESULTS:Myocardial infarctions induced increased left ventricular diastolic and systolic areas associated with a decreased fractional area change and a posterior wall shortening velocity. With regard to the extracellular matrix variables, the myocardial infarction group presented with higher values of periostin and types I and III collagen and higher interstitial collagen volume fractions and myocardial hydroxyproline concentrations. In addition, periostin was positively correlated with type III collagen levels (r = 0.673, p = 0.029) and diastolic (r = 0.678, p = 0.036) and systolic (r = 0.795, p = 0.006) left ventricular areas. Considering the relationship between periostin and the cardiac function variables, periostin was inversely correlated with both the fractional area change (r = -0.783, p = 0.008) and the posterior wall shortening velocity (r = -0.767, p = 0.012).CONCLUSIONS:Periostin might be a modulator of deleterious cardiac remodeling in the chronic phase after myocardial infarction in rats.

Periostin is Down-regulated during Periodontal Inflammation

Periostin, a matricellular adapter protein highly expressed by periodontal ligament fibroblasts, is implicated in the maintenance of periodontal integrity, which is compromised during periodontal diseases. The aim of this study was to explore the influence of chronic periodontal inflammation on tissue periostin levels. Periodontal breakdown was induced in a pre-clinical ligature periodontal inflammatory disease model. Periodontal tissue specimens were harvested at baseline, 2 weeks, and 4 weeks and prepared for histologic, immunofluorescence, and micro-CT examination. Statistical analyses were conducted by Kruskal-Wallis, Mann-Whitney, and Spearman’s tests. Periostin detection levels were reduced over time in response to the inflammatory process (1 ± 0.05; 0.67 ± 0.03; 0.31 ± 0.02; p < 0.001; baseline, 2, and 4 weeks, respectively). Simultaneously, alveolar bone loss increased from baseline to the 2- and 4-week time-points (0.40 ± 0.02 mm; 1.39 ± 0.08 mm; 1.33 ± 0.15 mm; p < 0.001), which was inversely correlated with the levels of periostin (ρ = -0.545; p < 0.001). In conclusion, periostin PDL tissue levels significantly decrease under chronic inflammatory response and correlate with the detrimental changes to the periodontium over time.

Extracellular matrix-mediated differentiation of periodontal progenitor cells

The periodontal ligament (PDL) is a specialized connective tissue that connects the surface of the tooth root with the bony tooth socket. The healthy PDL harbors stem cell niches and extracellular matrix (ECM) microenvironments that facilitate periodontal regeneration. During periodontal disease, the PDL is often compromised or destroyed, reducing the life-span of the tooth. In order to explore new approaches toward the regeneration of diseased periodontal tissues, we have tested the effect of periodontal ECM signals, fibroblast growth factor 2 (FGF2), connective tissue growth factor (CTGF), and the cell adhesion peptide Arg-Gly-Asp (RGD) on the differentiation of two types of periodontal progenitor cells, PDL progenitor cells (PDLPs) and dental follicle progenitor cells (DFCs). Our studies documented that CTGF and FGF2 significantly enhanced the expression of collagens I & III, biglycan and periostin in tissue engineered regenerates after 4 weeks compared to untreated controls. Specifically, CTGF promoted mature PDL-like tissue regeneration as demonstrated by dense periostin localization in collagen fiber bundles. CTGF and FGF2 displayed synergistic effects on collagen III and biglycan gene expression, while effects on mineralization were antagonistic to each other: CTGF promoted while FGF2 inhibited mineralization in PDL cell cultures. Incorporation of RGD peptides in hydrogel matrices significantly enhanced attachment, spreading, survival and mineralization of the encapsulated DFCs, suggesting that RGD additives might promote the use of hydrogels for periodontal mineralized tissue engineering. Together, our studies have documented the effect of three key components of the periodontal ECM on the differentiation of periodontal progenitor populations.