Overexpression Of Periostin Research Articles

Periostin regulates the activity of keloid fibroblasts by activating the JAK/STAT signaling pathway

A keloid is secondary to skin trauma or has spontaneously manifested as an overgrowth and occurs when the skin heals abnormally after an injury. The main pathological manifestations are abnormal proliferation of keloid fibroblasts (KEL-FIB). This study researched periostin (POSTN) on keloid fibroblasts (KEL-FIB) and the associated mechanism, aiming to provide a reference for the targeted therapy of keloid. We got tissues from Second People’s Hospital of Guangxi Zhuang Autonomous Region between June 2022 and March 2023. POSTN expression was increased in keloid skin tissue and KEL-FIB than normal skin tissue and normal fibroblasts. We collected and inoculated KEL-FIB cells, transfection of si-NC (Silencing of POSTN negative control), si-POSTN (Silencing of POSTN), pcDNA-NC (Overexpression of POSTN negative control), and POSTN (Overexpression of POSTN) (Thermo Fisher Scientific) used Lipofectamine 2000 transfection reagent. Wound closure, cell proliferation viability, migrated cell numbers, and POSTN, p-JAK2, p-STAT3 protein levels were reduced in the si-POSTN group. Wound closure, cell proliferation viability, migrated cell numbers, and POSTN, p-JAK2, p-STAT3 protein levels were elevated in the POSTN group. POSTN protein levels did not changed and wound closure, cell proliferation viability, migrated cell numbers, were reduced in the POSTN+S-Ruxolitinib group. The study results indicated that POSTN promotes cell migration and proliferation by activating the JAK/STAT pathway, promoting KEL-FIB development.

Periostin/Bone Morphogenetic Protein 1 axis axis regulates proliferation and osteogenic differentiation of sutured mesenchymal stem cells and affects coronal suture closure in the TWIST1+/− mouse model of craniosynostosis

Background and objectiveThe pathogenesis of coronal suture craniosynostosis is often attributed to the dysregulated cellular dynamics, particularly the excessive proliferation and abnormal osteogenic differentiation of suture cells. Despite its clinical significance, the molecular mechanims of this condition remain inadequately understood. This study is dedicated to exploring the influence of the Periostin/Bone Morphogenetic Protein 1 (BMP1) axis on the growth and osteogenic maturation of Suture Mesenchymal Stem Cells (SMSCs), which are pivotal in suture homeostasis. MethodsNeonatal TWIST Basic Helix-Loop-Helix Transcription Factor 1 heterozygous (TWIST1+/−) mice, aged one day, were subjected to adenoviral vector-mediated Periostin upregulation. To modulate Periostin/BMP1 levels in SMSCs, we employed siRNA and pcDNA 3.1 vectors. Histological and molecular characterizations, including hematoxylin and eosin staining, Western blot, and immunohistochemistry were employed to study suture closure phenotypes and protein expression patterns. Cellular assays, encompassing colony formation, 5-ethynyl-2'deoxyuridine, and wound healing tests were conducted to analyze SMSC proliferation and migration. Osteogenic differentiation was quantified using Alkaline Phosphatase (ALP) and Alizarin Red S (ARS) staining, while protein markers of proliferation and differentiation were evaluated by Western blotting. The direct interaction between Periostin and BMP1 was validated through co-immunoprecipitation assays.ResultsIn the TWIST1+/− model, an upregulation of Periostin coupled with a downregulation of BMP1 was observed. Augmenting Periostin expression mitigated craniosynostosis. In vitro, overexpression of Periostin or BMP1 knockdown suppressed SMSC proliferation, migration, and osteogenic differentiation. Periostin knockdown manifested an inverse biological impact. Notably, the suppressive influence of Periostin overexpression on SMSCs was effectively counteracted by upregulating BMP1. There was a direct interaction between Periostin and BMP1.ConclusionThese findings underscore the significance of the Periostin/BMP1 axis in regulating craniosynostosis and SMSC functions, providing new insights into the molecular mechanisms of craniosynostosis and potential targets for therapeutic intervention.

POSTN promotes granulosa cell proliferation in sheep follicles through focal adhesion

BackgroundThe complex regulatory mechanisms involved in follicular development in sheep are not fully understood. This study aimed to understand the expression of periostin (POSTN) in granulosa cells (GCs) and its effect on follicle development. MethodsThe effect of luteinizing hormone (LH) treatment on POSTN expression in GCs was examined. POSTN was overexpressed or inhibited in GCs, and its effects on cell proliferation and apoptosis, as well as potential mechanisms of action, were evaluated. ResultsPOSTN showed higher expression in ovarian tissue than in other tissues and higher expression in large follicles than in small follicles. LH treated GCs promoted POSTN expression. Overexpression of POSTN in GCs significantly increased cell proliferation and inhibited apoptosis. Phosphorylation levels of focal adhesion kinase and autophagy were elevated in POSTN overexpressing GCs. ConclusionPOSTN affects GCs proliferation and follicle development through the focal adhesion, potentially improving fecundity in sheep.

Irisin ameliorates UUO-induced renal interstitial fibrosis through TGF-β1/periostin/MMP-2 signaling pathway.

Renal fibrosis is the most common pathway in progressive kidney diseases. The unilateral ureteral obstruction (UUO) model is used to induce progressive renal fibrosis. We evaluated the effects of irisin on renal interstitial fibrosis in UUO mice. The GSE121190, GSE36496, GSE42303, and GSE96101 datasets were downloaded from the Gene Expression Omnibus (GEO) database. In total, 656 differentially expressed genes (DEGs) were identified in normal and UUO mouse renal samples. Periostin and matrix metalloproteinase-2 (MMP-2) were selected to evaluate the effect of irisin on renal fibrosis in UUO mice. In UUO mice, irisin ameliorated renal function, decreased the expression of periostin and MMP-2, and attenuated epithelial-mesenchymal transition and extracellular matrix deposition in renal tissues. In HK-2 cells, irisin treatment markedly attenuated TGF-β1-induced expression of periostin and MMP-2. Irisin treatment also inhibited TGF-β1-induced epithelial-mesenchymal transition, extracellular matrix formation, and inflammatory responses. These protective effects of irisin were abolished by the overexpression of periostin and MMP-2. In summary, irisin treatment can improve UUO-induced renal interstitial fibrosis through the TGF-β1/periostin/MMP-2 signaling pathway, suggesting that irisin may be used for the treatment of renal interstitial fibrosis.

Disrupted cardiac fibroblast BCAA catabolism contributes to diabetic cardiomyopathy via a periostin/NAP1L2/SIRT3 axis

BackgroundPeriostin is an extracellular matrix protein that plays a critical role in cell fate determination and tissue remodeling, but the underlying role and mechanism of periostin in diabetic cardiomyopathy (DCM) are far from clear. Thus, we aimed to clarify the mechanistic participation of periostin in DCM.MethodsThe expression of periostin was examined in DCM patients, diabetic mice and high glucose (HG)-exposed cardiac fibroblasts (CF). Gain- and loss-of-function experiments assessed the potential role of periostin in DCM pathogenesis. RNA sequencing was used to investigate the underlying mechanisms of periostin in DCM.ResultsA mouse cytokine antibody array showed that the protein expression of periostin was most significantly upregulated in diabetic mouse heart, and this increase was also observed in patients with DCM or HG-incubated CF. Periostin-deficient mice were protected from diabetes-induced cardiac dysfunction and myocardial damage, while overexpression of periostin held the opposite effects. Hyperglycemia stimulated the expression of periostin in a TGF-β/Smad-dependent manner. RNA sequencing results showed that periostin upregulated the expression of nucleosome assembly protein 1-like 2 (NAP1L2) which recruited SIRT3 to deacetylate H3K27ac on the promoters of the branched-chain amino acid (BCAA) catabolism-related enzymes BCAT2 and PP2Cm, resulting in BCAA catabolism impairment. Additionally, CF-derived periostin induced hypertrophy, oxidative injury and inflammation in primary cardiomyocytes. Finally, we identified that glucosyringic acid (GA) specifically targeted and inhibited periostin to ameliorate DCM.ConclusionOverall, manipulating periostin expression may function as a promising strategy in the treatment of DCM.

Periostin promotes extensive neovascularization in placenta accreta spectrum disorders via Notch signaling

Objective Extensive neovascularization, closely linked to massive intraoperative blood loss, is a pathological hallmark of placenta accreta spectrum (PAS) cases. This study aims to explore proteins related to neovascularization and elucidate their regulatory roles in PAS, enhancing our understanding of this condition. Methods The isobaric tags for relative and absolute quantitation technique were used to identify and quantify the differentially expressed proteins in placentas from PAS and healthy pregnant women. Immunofluorescence staining and western blot analysis were conducted to determine the protein expression and localization. Gain-of-function experiments were used to conduct cell proliferation and migration assays. In addition, the tube formation assay was performed to evaluate angiogenesis in vitro. The Notch inhibitor DAPT was used to determine the involvement of Notch signaling in angiogenesis in PAS. Results Periostin (POSTN) exhibited higher expression in PAS placentas than in normal placentas. Moreover, the overexpression of POSTN in endothelial cells promoted cell proliferation, mobility, and endothelial angiogenesis via the Notch signaling pathway in vitro. Conclusion Elevated POSTN expression in PAS is associated with increased angiogenesis, indicating its potential as a molecular marker for significant intraoperative blood loss.

Abnormal basement membrane results in increased keratinocyte-derived periostin expression in psoriasis similar to wound healing

The psoriatic skin resembles wound healing, and it shows abnormalities at the basement membrane (BM), also in the non-lesional skin. Fibroblast-derived dermal periostin has well-known functions in wound healing and Th2-mediated diseases, such as atopic dermatitis. Here we show that serum periostin level was elevated in psoriatic patients, remarkably in the systemically treated ones. Obvious periostin positivity was detected in basal keratinocytes of the non-lesional, lesional, and previously-lesional psoriatic vs. healthy skin. Ex vivo skin models were generated to examine how different skin injuries affect periostin expression during wound healing. Our newly developed cultured salt-split model demonstrated that BM-injury induced periostin expression in basal keratinocytes, and periostin levels in the supernatant were also increased upon healing. In wound healing models, β1-integrin expression was similarly induced. β1-integrin blocking caused reduced periostin expression in in vitro scratch assay, indicating that β1-integrin can mediate periostin production. In contrast to atopic dermatitis, psoriatic basal keratinocytes are in an activated state and show a stable wound healing-like phenotype with the overexpression of periostin. This abnormal BM-induced wound healing as a potential compensatory mechanism can be initiated already in the non-lesional skin present in the lesion and keratinocytes can remain activated in the healed skin.

The Effects of Periostin Expression on Fibroid-Like Transition of Myometrial Cells.

Fibroids, benign tumors of the myometrium, are the most common tumors in women and are associated with spontaneous abortion, preterm birth, placenta abruption, and infertility, among others. The incidence of fibroids in reproductive aged women is 20-89%. Fibroids are characterized by high production of extracellular matrix (ECM), particularly collagens, which play a role in their growth. However, their pathogenesis is poorly understood. Recently, we and others have found periostin (POSTN), a regulatory ECM protein, to be overexpressed in the majority of fibroids analyzed. Periostin is an ECM protein that is a critical regulator and well-established biomarker for fibrosis in tissues such as the lung, skin, and kidney. Our hypothesis was that periostin plays a role in the fibrotic transition of myometrial cells to fibroid cells. To test this, we evaluated the effects of POSTN overexpression in myometrial cells. Telomerase-immortalized myometrial cells were transduced with control or POSTN-overexpression lentivirus particles, generating one control (dCas9-Mock) and two overexpression (dCas9-POSTN-01, dCas9-POSTN-02) cell lines. Overexpression of POSTN in immortalized myometrial cells resulted in a change in phenotype consistent with fibroid cells. They upregulated expression of key fibroid genes and had increased proliferation, adhesion, and migration in vitro. Here, we show a potential role for periostin in the transition of myometrial cells to fibroid cells, giving rationale for future investigation into the role of periostin in fibroid pathogenesis and its potential as a therapeutic target.

The Prognostic Value of Periostin Expression in Non-Small Cell Lung Cancer: A Meta-Analysis.

BackgroundNon-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related death in the world and its poor prognosis is a major concern. Periostin was found to be associated with the prognosis of NSCLC. However, the research results were inconsistent. This meta-analysis evaluated the correlation between periostin expression and the prognosis of NSCLC.Material/MethodsA meta-analysis was performed on data acquired from PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Database from inception to 18 June 2022. Published and unpublished studies investigating the correlation between periostin expression and the prognosis of NSCLC were included in this meta-analysis. Eligible studies reported at least 1 of the following clinical outcome measures: overall survival, progression-free survival, cancer-specific survival, relapse-free survival, disease-free survival, or other clinical parameters of prognosis. Pooled hazard ratios (HR) with 95% confidence interval (CI) were calculated using the random-effects model. Sensitivity and subgroup analyses and assessment of publication bias were also conducted.ResultsThis meta-analysis enrolled 2504 NSCLC cases from 12 eligible studies. The hazard ratio for the overall survival was 1.761 (95% CI: 1.022–3.033, P=0.041). Heterogeneity was significant among the studies, but publication bias was lacking. Subgroup analyses were performed based on different issues, such as districts, antibodies and methods for periostin detection.ConclusionsOverexpression of periostin is a negative prognostic factor and is associated with worse overall survival (OS) in NSCLC patients. Periostin may serve as a prognostic biomarker for NSCLC patients.

MiRNAs-mediated overexpression of Periostin is correlated with poor prognosis and immune infiltration in lung squamous cell carcinoma.

Lung cancer is one of the most common malignancies with a high mortality rate worldwide. POSTN has been shown to be strongly correlated with the poor prognosis of lung cancer patients. However, the function and mechanism of action of POSTN in lung cancer remain unclear. Here, we carried out a pan-cancer analysis to assess the clinical prognostic value of POSTN based on the TCGA, TIMER, Oncomine, Kaplan-Meier, and UALCAN databases. We found that upregulated POSTN can be a promising biomarker to predict the prognosis of patients with lung cancer. High levels of POSTN correlated with immune cell infiltration in lung cancer, especially lung squamous cell carcinoma (LUSC), which was further confirmed based on the results from the TISIDB database. Moreover, the expression analysis, correlation analysis, and survival analysis revealed that POSTN-targeted miRNAs, downregulation of has-miR-144-3p and has-miR-30e-3p, were significantly linked to poor prognosis in patients with LUSC. Taken together, we identified that POSTN can act as a novel biomarker for determining the prognosis related to immune infiltration in patients with LUSC and deserves further research.

Periostin regulates LPS-induced apoptosis via Nrf2/HO-1 pathway in periodontal ligament fibroblasts.

Periostin is important for the maintenance of periodontal tissue, but its role in periodontitis is controversial. This research investigated the effect of periostin in periodontitis and the underlying mechanism. Mouse periodontitis models in vivo and inflammation model in vitro which were induced by Porphyromonas gingivalis lipopolysaccharide were established to evaluate periostin expression. Human periodontal ligament fibroblasts (PDLFs) were treated with lipopolysaccharide and N-acetylcysteine, fluorescence staining, flow cytometry, Western blot, and qRT-PCR were used to detect reactive oxygen species (ROS), periostin expression, and apoptosis-related makers. The periostin gene was successfully transfected into PDLFs to verify the effect of periostin on apoptosis. Then, the Nrf2 inhibitor was added to clarify the mechanism. Periostin expression decreased in the periodontal ligaments of mouse periodontitis models and lipopolysaccharide-induced PDLFs. Lipopolysaccharide promoted the activation of ROS and apoptosis in PDLFs, whereas N-acetylcysteine reversed this condition. Overexpression of periostin suppressed apoptosis of PDLFs and reversed the inhibitory effect of lipopolysaccharide on nuclear Nrf2 expression. Moreover, the Nrf2 inhibitor attenuated the protective effect of periostin on lipopolysaccharide-induced apoptosis. Lipopolysaccharide induced apoptosis in PDLFs by inhibiting periostin expression and thus Nrf2/HO-1 pathway, indicating that periostin could be a potential therapeutic target for periodontitis.

Silencing periostin inhibits myofibroblast transdifferentiation of fibrotic buccal mucosal fibroblasts

Oral submucous fibrosis (OSF) a well-recognized oral premalignant disorder. Several studies have demonstrated that periostin, a matricellular protein, is involved in the development and pathogenesis of fibrosis diseases. Nevertheless, the contribution of periostin in OSF remains to be uncovered. The purpose of the study was to illustrate the functional role of periostin involved in OSF pathogenesis. RNA-sequencing was employed to screen for differentially expressed genes in normal and OSF tissues. Validation of the upregulation of periostin in OSF specimens and fibrotic buccal mucosal fibroblasts (fBMFs) was conducted by qRT-PCR. The correlation of the gene expression of periostin and various fibrosis markers was analyzed. In addition, the functional role of periostin in myofibroblast features was tested using collagen gel contraction and transwell migration assays. We observed overexpression of periostin in OSF specimens using RNA-sequencing and confirmed its upregulation in OSF tissues and patient-derived fBMFs. Besides, there was a positive relationship between the expression of periostin and several fibrosis-associated markers, including ACTA2 (α-smooth muscle actin; α-SMA), COL1A1 (type 1 collagen α1 chain), TGFB1 (TGF-β1), and FN1 (fibronectin). Furthermore, we examined the effect of silencing periostin on the maintenance of myofibroblast characteristics and showed that knockdown of periostin suppressed the expression of α-SMA. Also, inhibition of periostin markedly downregulated the myofibroblast activities (collagen gel contraction and migration capacities). Our results indicate the aberrant expression of periostin in OSF tissues and myofibroblasts. Moreover, the expression of periostin is positively associated with fibrosis markers, and repression of periostin may be a promising direction to alleviate the progression of OSF.

Over-expression of stromal periostin correlates with poor prognosis of cutaneous squamous cell carcinomas.

Periostin, an extracellular matrix macromolecule implicated in tumorigenesis, serves as a prognostic marker for many cancer types. However, there are no data on periostin expression in cutaneous squamous cell carcinoma (cSCC). This study examined periostin expression in patients with cSCC and explored its clincopathological relationship and prognosis. Using immunohistochemistry and ImageJ analysis, we compared periostin expression in 95 cSCCs across a spectrum of cSCC aggressiveness: cSCC in situ (SCCIS) (n=25), low-risk cSCC (LR-cSCC) (n=26), high-risk cSCC (HR-cSCC) (n=38), and cSCC in recessive dystrophic epidermolysis bullosa patients (RDEB cSCC) (n=6). Immunohistochemistry demonstrated periostin expression within the intra-tumoral stroma but not within tumor cells. Periostin levels significantly (P<0.001) increased from SCCIS, LR-cSCC, HR-cSCC to RDEB SCC. The stroma of most of the cSCCs we evaluated contained cancer-associated fibroblasts with a myofibroblastic (α -SMA-positive) phenotype. Co-localization of periostin with α-SMA, evidence of fibroblast periostin expression, and absence of keratinocyte or tumor cell periostin expression suggest that, in cSCC, periostin is a product of the peritumoral microenvironment and not the tumor cells themselves. Our data indicate that fibroblast periostin expression is highly correlated with the aggressiveness of cSCC, and may thereby provide a molecular marker that will be useful for subtyping and diagnosing cSCCs according to their biological nature.

POSTN promotes proliferation and epithelial-mesenchymal transition in renal cell carcinoma through ILK/AKT/mTOR pathway.

Periostin (POSTN) is an extracellular matrix (ECM) protein, involved in various diseases. This research focused on the detailed mechanisms study of periostin (POSTN) overexpression in renal cell carcinoma (RCC) invasion and migration. Western blot and RT-PCR were performed to explore POSTN expression in various RCC cells. Cells were transfected with siRNAs or lentivirus to regulate the expression of POSTN. The effects of POSTN on cell viability, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT) of RCC cells were determined by CCK-8, flow cytometry, migration and invasion assay and Western blot analysis. POSTN expression was significantly enhanced in RCC cells compared with renal tubular epithelial cells. In vitro experiments showed that POSTN knockdown could dramatically inhibit RCC cell proliferation, migration and invasion, while overexpression of POSTN could promote these biological behaviors. We further demonstrated that POSTN knockdown suppressed epithelial-mesenchymal transition (EMT), which was mediated via upregulation of E-cadherin and downregulation of N-cadherin and vimentin, through IKL/AKT/mTOR pathway. In contrast, overexpression of POSTN could promote EMT in RCC cells via the activation of IKL /AKT/mTOR pathway. Next, we demonstrated that higher POSTN expression promoted angiogenesis in vivo in an RCC xenograft tumor via activating IKL /AKT/mTOR pathway. Our study showed that POSTN could promote EMT through ILK/AKT/mTOR pathway and might be an alternative therapeutic strategy for RCC treatment.

Periostin regulates osteogenesis of mesenchymal stem cells from ovariectomized rats through actions on the ILK/Akt/GSK-3β Axis.

Osteoporosis is a condition of the skeleton that mainly results from estrogen deficiency. Periostin is a matricellular component in bone that is involved in osteoblast differentiation. However, how Periostin promotes osteogenesis remains largely unknown. Here, we isolated bone marrow skeletal stem cells (BMSCs) derived from an ovariectomy (OVX)-induced osteoporosis rat model and the effects of periostin on BMSCs derived from OVX rats (OVX-BMSCs) were assessed. Overexpression of periostin enhanced alkaline phosphatase (ALP) and alizarin red staining in OVX-BMSCs as well as the osteogenic genes OCN, BSP and Runx2. ILK is a downstream effector of signals from the extracellular matrix and participates in bone homeostasis. Overexpression of periostin also increased expression of protein levels for ILK, as well as the downstream targets pAkt and pGSK3β. Suppression of ILK or Akt partially suppressed the enhancement of osteogenic ability induced by periostin overexpression in OVX-BMSCs. Thus, periostin may promote the osteogenic ability of OVX-BMSCs through actions on the ILK/Akt/GSK3β axis.

Periostin Promotes Cell Proliferation and Macrophage Polarization to Drive Repair after AKI.

The matricellular protein periostin has been associated with CKD progression in animal models and human biopsy specimens. Periostin functions by interacting with extracellular matrix components to drive collagen fibrillogenesis and remodeling or by signaling through cell-surface integrin receptors to promote cell adhesion, migration, and proliferation. However, its role in AKI is unknown. We used mice with conditional tubule-specific overexpression of periostin or knockout mice lacking periostin expression in the renal ischemia-reperfusion injury model, and primary cultures of isolated tubular cells in a hypoxia-reoxygenation model. Tubular epithelial cells showed strong production of periostin during the repair phase of ischemia reperfusion. Periostin overexpression protected mice from renal injury compared with controls, whereas knockout mice showed increased tubular injury and deteriorated renal function. Periostin interacted with its receptor, integrin-β1, to inhibit tubular cell cycle arrest and apoptosis in in vivo and in vitro models. After ischemia-reperfusion injury, periostin-overexpressing mice exhibited diminished expression of proinflammatory molecules and had more F4/80+ macrophages compared with knockout mice. Macrophages from periostin-overexpressing mice showed increased proliferation and expression of proregenerative factors after ischemia-reperfusion injury, whereas knockout mice exhibited the opposite. Coculturing a macrophage cell line with hypoxia-treated primary tubules overexpressing periostin, or treating such macrophages with recombinant periostin, directly induced macrophage proliferation and expression of proregenerative molecules. In contrast to the detrimental role of periostin in CKD, we discovered a protective role of periostin in AKI. Our findings suggest periostin may be a novel and important mediator of mechanisms controlling renal repair after AKI.

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.

Overexpression of periostin is positively associated with gastric cancer metastasis through promoting tumor metastasis and invasion.

Gastric tumors generally have a poor prognosis and molecular markers to improve early detection and predict outcomes are greatly needed. The present study reports that periostin (POSTN), a secretory protein that can alter the remodeling of the extracellular matrix, is highly expressed in gastric tumors. Gastric tissues were collected from patients at the Department of Thoracic Surgery/Huiqiao Medical Center, Nanfang Hospital, Southern Medical University. These patients provided an informed consent and were approved by the institute. Normal, cancer, and metastatic gastric tissues from lymph nodes and tissues adjacent to the tumor were collected from patients diagnosed with gastric cancer. Periostin expression gradually increased as the risk grade of the NIH classification increased, and this was closely correlated with disease-free survival and overall survival. Compared with adjacent normal gastric mucosa tissues, protein expression of POSTN in gastric cancer tissues and metastases was significantly higher by immunohistochemistry and Western blot analysis. In addition, POSTN was upregulated in advanced gastric cancer tissues than in early gastric cancer tissues. Moreover, the ectopic expression of POSTN in the immortalized human gastric cell line could increase the metastasis and invasion of gastric cancer cells. The present results could establish the significance of POSTN in driving oncogenesis and metastasis in gastric tumors, with implications for its potential use as a diagnostic or prognostic biomarker, and as a candidate therapeutic target.

Periostin overexpression in collecting ducts accelerates renal cyst growth and fibrosis in polycystic kidney disease

In polycystic kidney disease (PKD), persistent activation of cell proliferation and matrix production contributes to cyst growth and fibrosis, leading to progressive deterioration of renal function. Previously, we showed that periostin, a matricellular protein involved in tissue repair, is overexpressed by cystic epithelial cells of PKD kidneys. Periostin binds αVβ3-integrins and activates integrin-linked kinase (ILK), leading to Akt/mammalian target of rapamycin (mTOR)-mediated proliferation of human PKD cells. By contrast, periostin does not stimulate the proliferation of normal human kidney cells. This difference in the response to periostin is due to elevated expression of αVβ3-integrins by cystic cells. To determine whether periostin accelerates cyst growth and fibrosis, we generated mice with conditional overexpression of periostin in the collecting ducts (CDs). Ectopic CD expression of periostin was not sufficient to induce cyst formation or fibrosis in wild-type mice. However, periostin overexpression in pcy/pcy ( pcy) kidneys significantly increased mTOR activity, cell proliferation, cyst growth, and interstitial fibrosis; and accelerated the decline in renal function. Moreover, CD-specific overexpression of periostin caused a decrease in the survival of pcy mice. These pathological changes were accompanied by increased renal expression of vimentin, α-smooth muscle actin, and type I collagen. We also found that periostin increased gene expression of pathways involved in repair, including integrin and growth factor signaling and ECM production, and it stimulated focal adhesion kinase, Rho GTPase, cytoskeletal reorganization, and migration of PKD cells. These results suggest that periostin stimulates signaling pathways involved in an abnormal tissue repair process that contributes to cyst growth and fibrosis in PKD.