Cellular Communication Networks Research Articles

D2D Communication in a 5G mm-Wave Cellular Network for Wireless Sensor Networks

D2D Communication in a 5G mm-Wave Cellular Network for Wireless Sensor Networks

Optimal resource allocation strategy for integrated sensing and communication cellular network with multiple user demands

AbstractFuture communication networks are widely considered to be able to provide both high‐speed communication service and reliable sensing service. Integrated sensing and communication (ISAC) is considered to be the key technology to realize this vision. Appropriate resource allocation strategy is essential for ensuring the quality of both communication and sensing services in terms of ISAC. Existing ISAC‐based resource allocation schemes mainly focus on the coexistence of sensing and communication. However, in multi‐user ISAC networks, the services required by users are diverse, including sensing‐only, communication‐only and dual‐function cases. To this end, a resource allocation strategy is proposed based on user quality of service (QoS). Specifically, the sum rate of cellular network is maximized via optimizing spectrum resource selection and transmit power, while satisfying the sensing QoS. The optimal solution to the entire problem is achieved by first demonstrating that the communication rate in this paper is a monotonically increasing function of sensing power, which allows to obtain the optimal power allocation scheme. Subsequently, a matching method is employed to obtain the optimal spectrum sharing scheme. Numerical results validate the effectiveness of the proposed algorithm and also unveil a flexible trade‐off in ISAC systems over the benchmark scheme.

Transient analysis of energy-saving strategy for cognitive radio networks using G-queue with heterogeneity

Energy efficiency, high data speeds, and effective spectrum utilization stand as the primary factors governing 5G and beyond networks. A base station (BS) in a cognitive radio network (CRN) that conserves energy during sleep periods is a promising contender for achieving more effective spectrum allocation. An efficient energy-saving strategy is offered in this study to achieve greener communication in wireless cellular networks. This study aims to propose and analyze an energy-saving scheme for the BS, taking into account the heterogeneity and reliability of networks. The entire system is modeled as a three-dimensional Markov chain by establishing a discrete-time preemptive priority queueing model with single vacation, heterogeneous packets, and negative packets such as viruses. Then, the transient analysis of the Markov chain is performed using the recursive method. Utilizing the transient probability distribution, we present numerical results derived from reliability analysis and queueing analysis to substantiate the validity of the proposed model. Furthermore, results based on the energy-saving degree are showcased to affirm the effectiveness of the proposed scheme. Finally, a reward cost function is obtained depending on the successful transmission of secondary packets, and the Quasi-Newton method is used to determine the optimal reward cost.

Single-Cell RNA Sequencing Reveals the Cellular Landscape of Longissimus Dorsi in a Newborn Suhuai Pig.

The introduction of single-cell RNA sequencing (scRNA-seq) technology has spurred additional advancements in analyzing the cellular composition of tissues. The longissimus dorsi (LD) in pigs serves as the primary skeletal muscle for studying meat quality in the pig industry. However, the single-cell profile of porcine LD is still in its infancy stage. In this study, we profiled the transcriptomes of 16,018 cells in the LD of a newborn Suhuai pig at single-cell resolution. Subsequently, we constructed a cellular atlas of the LD, identifying 11 distinct cell populations, including endothelial cells (24.39%), myotubes (18.82%), fibro-adipogenic progenitors (FAPs, 18.11%), satellite cells (16.74%), myoblasts (3.99%), myocytes (5.74%), Schwann cells (3.81%), smooth muscle cells (3.22%), dendritic cells (2.99%), pericytes (1.86%), and neutrophils (0.33%). CellChat was employed to deduce the cell-cell interactions by evaluating the gene expression of receptor-ligand pairs across different cell types. The results show that FAPs and pericytes are the primary signal contributors in LD. In addition, we delineated the developmental trajectory of myogenic cells and examined alterations in the expression of various marker genes and molecular events throughout various stages of differentiation. Moreover, we found that FAPs can be divided into three subclusters (NR2F2-FAPs, LPL-FAPs, and TNMD-FAPs) according to their biological functions, suggesting that the FAPs could be associated with the differentiation of tendon cell. Taken together, we constructed the cellular atlas and cell communication network in LD of a newborn Suhuai pig, and analyzed the developmental trajectory of myogenic cells and the heterogeneity of FAPs subpopulation cells. This enhances our comprehension of the molecular features involved in skeletal muscle development and the meat quality control in pigs.

Examining the function of macrophage oxidative stress response and immune system in glioblastoma multiforme through analysis of single-cell transcriptomics.

Glioblastoma (GBM), a prevalent malignant neoplasm within the neuro-oncological domain, has been a subject of considerable scrutiny. Macrophages, serving as the principal immunological constituents, profoundly infiltrate the microenvironment of GBM. However, investigations elucidating the intricate immunological mechanisms governing macrophage involvement in GBM at the single-cell level remain notably limited. We conducted a comprehensive investigation employing single-cell analysis, aiming to redefine the intricate cellular landscape within both the core and peripheral regions of GBM tumors. Our analytical focus extended to the profound study of macrophages, elucidating their roles within the context of oxidative stress, intercellular information exchange, and cellular trajectories concerning GBM and its assorted subpopulations. We pursued the identification of GBM prognostic genes intricately associated with macrophages. Utilizing experimental research to investigate the relevance of MANBA in the context of GBM. Our investigations have illuminated the central role of macrophages in the intricate interplay among various subpopulations within the GBM microenvironment. Notably, we observed a pronounced intensity of oxidative stress responses within macrophages when compared to their GBM counterparts in other subpopulations. Moreover, macrophages orchestrated intricate cellular communication networks, facilitated by the SPP1-CD44 axis, both internally and with neighboring subpopulations. These findings collectively suggest the potential for macrophage polarization from an M1 to an M2 phenotype, contributing to immune suppression within the tumor microenvironment. Furthermore, our exploration unearthed GBM prognostic genes closely associated with macrophages, most notably MANBA and TCF12. Remarkably, MANBA appears to participate in the modulation of neuroimmune functionality by exerting inhibitory effects on M1-polarized macrophages, thereby fostering tumor progression. To bolster these assertions, experimental validations unequivocally affirmed the promotional impact of MANBA on GBM, elucidated through its capacity to curb cell proliferation, invasiveness, and metastatic potential. These revelations represent a pivotal step towards unraveling the intricate immunological mechanisms governing the interactions between macrophages and diverse subpopulations within the GBM milieu. Furthermore, they lay the foundation for the development of an innovative GBM prognostic model, with MANBA at its epicenter, and underscore the potential for novel immunotherapeutic targets in the ongoing pursuit of enhanced treatment modalities for this formidable malignancy.

CCN3/NOV inhibition attenuates oxidative stress-induced apoptosis of mouse neural stem/progenitor cells by blocking the activation of p38 MAPK: An in vitro study

Neural stem/progenitor cells (NSPCs) hold immense promise in clinical applications, yet the harsh conditions resulting from central nervous system (CNS) injuries, particularly oxidative stress, lead to the demise of both native and transplanted NSPCs. Cellular communication network factor 3 (CCN3) exhibits a protective effect against oxidative stress in various cell types. This study investigates the impact of CCN3 on NSPCs apoptosis induced by oxidative stress. To establish models of primary cultured mouse NSPCs under oxidative stress, we exposed them to 50 μM H2O2 for 4 h. Remarkably, pre-exposing CCN3 exacerbated the H2O2-induced decline in cell viability in a concentration-dependent manner. However, employing gene-targeted siRNA to inhibit CCN3 protected NSPCs against H2O2-induced cell death. Conversely, CCN3 replenishment reversed this protective effect, as evidenced by TUNEL staining, the ratio of Cleaved-caspase-3 to Pro-caspase-3, and Bcl-2/Bax. Further investigations revealed that CCN3 pretreatment increased the phosphorylation level of p38 MAPK, while silencing CCN3 diminished p38 MAPK activation. Ultimately, the impact of changes in CCN3 protein expression on H2O2-induced apoptosis was nullified using anisomycin (a p38 activator) and SB 203580 (a p38 inhibitor). Our findings suggest that CCN3 inhibition prevents H2O2-induced cell death in cultured mouse NSPCs via the p38 pathway. These discoveries may contribute to the development of strategies aimed at enhancing the survival of both endogenous and transplanted NSPCs following CNS oxidative stress insults.

Blockchain based mobile communication data privacy protection algorithm for cellular networks

The rapid development of mobile communication technology not only brings great convenience to users, but also brings the risk of user data privacy leakage. Due to the broadcasting nature of mobile communication transmission, open wireless interfaces have become a security vulnerability for mobile devices such as mobile phones, which can be easily eavesdropped. This article studied a data privacy protection algorithm suitable for mobile communication in cellular networks based on the anonymous mechanism of blockchain. This article first analyzes the overall framework and anonymity technology of blockchain data from the perspective of privacy and queryability. Then, based on blockchain technology, consistency mechanisms, privacy control, and access rights management are designed. Finally, mobile communication data privacy protection algorithms are designed and implemented through data encryption and verification. The latency of transactions under different task volumes and throughput at different nodes were analyzed to verify the reliability of several anonymous mechanisms in cellular network mobile communication data privacy protection in blockchain. Based on the experimental results, it was concluded that the reliability range of CryptoNote and the zero coin and zero currency protocol mechanism in the specified nodes was between 92 and 99%. This article utilized blockchain technology to distribute mobile communication data in nodes and achieve decentralized data transmission, thus protecting the privacy of wireless network communication data. By analyzing the reliability of anonymous mechanisms based on blockchain in mobile communication nodes, it was concluded that this method had certain research value.

Renewable energy electric sources as a support for multilevel cellular communication networks in various environment conditions – case study

Renewable energy electric sources as a support for multilevel cellular communication networks in various environment conditions – case study

A Novel Resource Sharing Scheme for Vehicular Communication in 5G Cellular Networks for Smart Cities

A Novel Resource Sharing Scheme for Vehicular Communication in 5G Cellular Networks for Smart Cities

Spatial and Single-Cell Investigations Illuminate Theragnostic value and Immune Landscape of Mitochondrial Dynamin-Like GTPase in Breast Cancer.

Background: As we delve into the intricate world of mitochondrial inner membrane proteins, particularly Optic Atrophy types 1 and 3 (OPA1/3), we uncover their pivotal role in maintaining mitochondrial dynamic equilibrium and fusion, crucial for cellular energy production and synthesis. Despite extensive scrutiny, the significance of OPA1/3 in breast cancer (BRCA) and its interplay with the immune microenvironment remain elusive. Materials and Methods: We meticulously sourced BRCA data from renowned repositories such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO), and the Human Protein Atlas (HPA), leveraging cutting-edge techniques including single-cell RNA-sequencing (scRNA-seq), spatial transcriptomics, and pharmacogenomics. Through multifaceted data analysis, we endeavored to unravel the intricate role and potential value of OPA1/3 in BRCA tumorigenesis and progression. Results: Our investigation reveals a conspicuous upregulation of OPA1/3 expression in BRCA, correlating with dismal prognoses. Kaplan-Meier plot analysis underscores that heightened OPA1/3 levels are associated with poor survival rates. Both clinical specimens and biobank biopsies corroborate the elevated expression of OPA1/3 in breast cancer patients. Moreover, scRNA-seq unveils a strong correlation between OPA1/3 and macrophage infiltration in the BRCA immune milieu, alongside its association with the cellular communication network involving CXCL, TGFb, VEGF, and IL16. Conclusion: In light of these findings, OPA1/3 emerges as a promising contender for therapeutic targeting and as a potential diagnostic, prognostic, and survival biomarker in BRCA. The implications of our study underscore the pressing need to explore these novel biomarkers to enhance patient outcomes.

Mechanical stimulation promotes fibrochondrocyte proliferation by activating the TRPV4 signaling pathway during tendon-bone insertion healing: CCN2 plays an important regulatory role.

We previously confirmed that mechanical stimulation is an important factor in the repair of tendon-bone insertion (TBI) injuries and that mechanoreceptors such as transient receptor potential ion-channel subfamily V member 4 (TRPV4; also known as transient receptor potential vanilloid 4) are key to transforming mechanical stimulation into intracellular biochemical signals. This study aims to elucidate the mechanism of mechanical stimulation regulating TRPV4. Immunohistochemical staining and western blotting were used to evaluate cartilage repair at the TBI after injury. The RNA expression and protein expression of mechanoreceptors and key pathway molecules regulating cartilage proliferation were analyzed. TBI samples were collected for transcriptome sequencing to detect gene expression. Calcium-ion imaging and flow cytometry were used to evaluate the function of TPRV4 and cellular communication network factor 2 (CCN2) after the administration of siRNA, recombinant adenovirus and agonists. We found that treadmill training improved the quality of TBI healing and enhanced fibrochondrocyte proliferation. The transcriptome sequencing results suggested that the elevated expression of the mechanistically stimulated regulator CCN2 and the exogenous administration of recombinant human CCN2 significantly promoted TRPV4 protein expression and fibrochondrocyte proliferation. In vitro, under mechanical stimulation conditions, small interfering RNA (siRNA)-CCN2 not only inhibited the proliferation of primary fibrochondrocytes but also suppressed TRPV4 protein expression and activity. Subsequently, primary fibrochondrocytes were treated with the TRPV4 agonist GSK1016790A and the recombinant adenovirus TRPV4 (Ad-TRPV4), and GSK1016790A partially reversed the inhibitory effect of siRNA-CCN2. The phosphoinositide 3-kinase/ protein kinase B (PI3K/AKT) signaling pathway participated in the above process. Mechanical stimulation promoted fibrochondrocyte proliferation and TBI healing by activating TRPV4 channels and the PI3K/AKT signaling pathway, and CCN2 may be a key regulatory protein in maintaining TRPV4 activation.

Interference Management Using Distance-based Clustering Method for D2D Communication Underlaying Multicell Cellular Network

Device-to-Device (D2D) communication is a technology candidate to support the next generation of cellular communication networks. D2D has the potential to boost the efficiency of frequency resources and system capacity. Generally, D2D performs in-band underlaying or shares frequency channels with traditional cellular users, which can cause co-channel interference problems between these two types of users. This paper offers a solution through a clustering technique for D2D users (DUEs) to reduce interference among DUEs. Clustering technique is performed on DUEs by allocating different frequency channels in a group, in order to reduce the interference effects experienced. Thus, it is expected that through this proposed method, both D2D and cellular users can experience better signal quality with minimal interference effects. Two systems have been considered i.e., the conventional/baseline system and the system with the proposed clustering method. The simulation results show that the SINR (Signal to Interference plus Noise Ratio) values and throughput for the proposed system compared to the baseline system has increased. The SINR result obtained is 16.8 dB for the baseline system and 17.68 dB for the proposed system, and resulting an improvement of 5.4%. Therefore, applying the proposed clustering method is able to increase acceptability of the desired signals for the observed DUEs. Then, the throughput value also increases by 5%, i.e., from 56.17 to 59 Mbps, which the system with the proposed clustering method provides a better increase in data transmission speed compared to the baseline system.

Construction of Multi‐Module RNA Nanoparticles Harboring miRNA, AIE, and CH6 Aptamer for Bone Targeting and Bone Anabolic Therapy

AbstractBone healing remains a major challenge in the treatment of osteoporosis. Effective strategies that simultaneously promote bone formation and inhibit bone resorption are crucial for the treatment of osteoporosis and associated bone defects. MicroRNA (miRNA)‐based approaches aim at simultaneously promoting bone formation and suppressing bone resorption and have therapeutic potential. However, the toxicity of cationic carriers and off‐target effects are two major challenges associated with miRNA delivery. This study establishes a bone‐targeting miRNA delivery system (CH6‐SNA‐26a) that integrates aggregation‐induced emission (AIE), a CH6 aptamer, and miRNAs into a single nanoplatform without any cationic carrier. In this system, an AIE molecule is coupled to miR‐26a to form a core–shell spherical nucleic acid (SNA‐26a). The CH6 aptamer is co‐assembled with the SNA to achieve specific miR‐26a delivery to the bone surface. This aptamer‐functionalized, non‐cationic miR‐26a delivery strategy (CH6‐SNA‐26a) enables both bone‐targeted delivery and high transfection efficiency, ultimately optimizing bone remodeling and calvarial bone healing in an osteoporosis mouse model while limiting adverse effects in non‐skeletal tissues. Mechanistically, the overexpression of CH6‐SNA‐26a in skeletal tissues promotes bone anabolic action by functionally targeting glycogen synthase kinase 3 beta in bone marrow mesenchymal stem cells and cellular communication network 2 in osteoclasts.

Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors.

S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes.

Performance analysis in SWIPT-based bidirectional D2D communications in cellular networks

Performance analysis in SWIPT-based bidirectional D2D communications in cellular networks

The Simple prEservatioN of Single cElls method for cryopreservation enables the generation of single-cell immune profiles from whole blood.

Current multistep methods utilized for preparing and cryopreserving single-cell suspensions from blood samples for single-cell RNA sequencing (scRNA-seq) are time-consuming, requiring trained personnel and special equipment, so limiting their clinical adoption. We developed a method, Simple prEservatioN of Single cElls (SENSE), for single-step cryopreservation of whole blood (WB) along with granulocyte depletion during single-cell assay, to generate high quality single-cell profiles (SCP). WB was cryopreserved using the SENSE method and peripheral blood mononuclear cells (PBMCs) were isolated and cryopreserved using the traditional density-gradient method (PBMC method) from the same blood sample (n=6). The SCPs obtained from both methods were processed using a similar pipeline and quality control parameters. Further, entropy calculation, differential gene expression, and cellular communication analysis were performed to compare cell types and subtypes from both methods. Highly viable (86.3 ± 1.51%) single-cell suspensions (22,353 cells) were obtained from the six WB samples cryopreserved using the SENSE method. In-depth characterization of the scRNA-seq datasets from the samples processed with the SENSE method yielded high-quality profiles of lymphoid and myeloid cell types which were in concordance with the profiles obtained with classical multistep PBMC method processed samples. Additionally, the SENSE method cryopreserved samples exhibited significantly higher T-cell enrichment, enabling deeper characterization of T-cell subtypes. Overall, the SENSE and PBMC methods processed samples exhibited transcriptional, and cellular communication network level similarities across cell types with no batch effect except in myeloid lineage cells. Comparative analysis of scRNA-seq datasets obtained with the two cryopreservation methods i.e., SENSE and PBMC methods, yielded similar cellular and molecular profiles, confirming the suitability of the former method's incorporation in clinics/labs for cryopreserving and obtaining high-quality single-cells for conducting critical translational research.

Rescue of murine hind limb ischemia via angiogenesis and lymphangiogenesis promoted by cellular communication network factor 2

Critical limb ischemia (CLI) is caused by severe arterial blockage with reduction of blood flow. The aim of this study was to determine whether therapeutic angiogenesis using cellular communication network factor 2 (CCN2) would be useful for treating CLI in an animal model. Recombinant CCN2 was administered intramuscularly to male C57BL/6J mice with hind limb ischemia. The therapeutic effect was evaluated by monitoring blood flow in the ischemic hind limb. In an in vivo assay, CCN2 restored blood flow in the ischemic hind limb by promoting both angiogenesis and lymphangiogenesis. VEGF-A and VEGF-C expression levels increased in the ischemic limb after treatment with CCN2. In an in vitro assay, CCN2 promoted proliferation of vascular and lymphatic endothelial cells, and it upregulated expression of Tgfb1 followed by expression of Vegfc and Vegfr3 in lymphatic endothelial cells under hypoxia. Suppression of Tgfb1 did not affect the activity of CCN2, activation of the TGF-β/SMAD signaling pathway, or expression of Vegfr3 in lymphatic endothelial cells. In summary, treatment using recombinant CCN2 could be a promising therapeutic strategy for CLI.

Correlation of the novel biomarker cellular communication network factor 1 (CCN1) with miR-155 in serum of patients with dilated cardiomyopathy

Abstract Background We recently reported an independent prognostic ability of serum CCN1 to predict all-cause mortality in DCM, irrespective of its aetiology (inflammatory DCM (DCMi) or conventional DCM). Interestingly, CCN1 levels were lower in patients with DCMi than in patients with conventional DCM. In a murine model, miR-155, which has key functions in inflammation, repressed the expression of CCN1 and impeded its function in angiogenesis. In a recent study, patients with DCMi had higher miR-155 plasma levels than those with conventional DCM. Purpose The present study evaluated whether circulating levels of CCN1 and miR-155 are associated in order to provide insight into the underlying pathophysiology. Methods Patients with a primary diagnosis of DCM, defined as LVEF <45% and an increased LVEDD (according to HENRY >117%), were included in this single-centre study. Exclusion criteria comprised primary valvular diseases (≥ second degree), acute myocarditis, active infectious diseases, pulmonary diseases, cancer, chronic alcoholism, and heart failure of other origins. CCN1 levels were determined in serum at study inclusion using an enzyme-linked immunosorbent assay. miR-155-5p was measured in serum using quantitative real-time PCR and normalized to a spike-in of miR-39-3p from C. elegans for analysis. The primary endpoint was all-cause mortality during follow-up. An adjusted multivariable Cox regression model (comprising age, sex, time of symptoms, LVEF, eGFR, CRP, and NT-proBNP) was used to assess the association between CCN1 or miR-155 with all-cause mortality. Results Among 283 patients in the DCM cohort with CCN1 data, miR-155 measurements were available for analysis in 270 patients. Among those, 77.4% were males at a median age of 55.3 [IQR 47.8, 64.7] years with 3.84 [IQR 1.1, 19.3] months since onset of disease who had severely reduced LVEF (31 [IQR 26, 37] %), elevated LVEDD (67 [IQR 62, 72] mm), and normal eGFR (CKD-EPI) (91.5 [IQR 74.01, 103.3] ml/min). During a median follow-up of 12.4 [IQR 10.5, 13.9] years, a total of 101 (37.4%) patients died. There was no significant difference in miR-155 levels between DCMi and conventional DCM (ΔCt: 14.84 vs 14.94, P = 0.60; and ΔΔCt values 1.68 vs 1.49, P = 0.42). A positive correlation was found for miR-155 (relative expression ΔΔCt values) with CCN1 in serum from patients with conventional DCM (rS = 0.251, p = 0.002) but not with DCMi (rS = 0.007, p = 0.94) (Figure 1). Unlike CCN1 (HR 1.11; 95% CI 1.04, 1.19; p = 0.002), miR-155 was not associated with all-cause mortality (HR 0.95; 95% CI 0.82, 1.11; P = 0.54) in adjusted multivariable Cox regression models. Conclusion A differential correlation of miR-155 with CCN1 levels was found in patients with conventional DCM vs. those with DCMi, suggesting a potential role of these biomarkers only in conventional DCM. Further investigation of the pathophysiology of CCN1 in DCM is warranted, including -omics analyses.

Antifibrotic effect of apremilast in systemic sclerosis dermal fibroblasts and bleomycin-induced mouse model

Phosphodiesterase (PDE) 4 inhibitors have been reported to suppress the progression of dermal fibrosis in patients with systemic sclerosis (SSc); however, the precise mechanisms remain to be elucidated. Therefore, we conducted experiments focusing on the antifibrotic and anti-inflammatory effects of apremilast using dermal fibroblasts derived from patients with SSc and an SSc mouse model. Dermal fibroblasts derived from healthy controls and patients with SSc were incubated with apremilast in the presence or absence of 10 ng/ml transforming growth factor (TGF)-β1 for the measurement of intracellular cAMP levels and evaluation of mRNA and protein expression. A bleomycin-induced dermal fibrosis mouse model was used to evaluate the inhibitory effects of apremilast on the progression of dermal fibrosis. Intracellular cAMP levels were significantly reduced in dermal fibroblasts derived from patients with SSc compared with those derived from healthy controls. Apremilast reduced the mRNA expression of profibrotic markers and the protein expression of type I collagen and Cellular Communication Network Factor 2 (CCN2) in dermal fibroblasts. Additionally, apremilast inhibited the progression of dermal fibrosis in mice, partly by acting on T cells. These results suggest that apremilast may be a potential candidate for treating dermal fibrosis in SSc.

Abstract 17425: Matricellular Protein CCN1 Modulates Post-Infarct Scar Integrity and Structure

Introduction: Collagen deposition is required for repair of the heart following myocardial infarction (MI). As collagen abundance increases, so does its alignment, potentially influencing scar integrity. Because cell-matrix interactions regulate fibroblast behavior and matrix dynamics, adhesive factors, like cellular communication network (CCN) proteins, may contribute to post-MI scar formation. CCN1's role in skin collagen modulation and its recent emergence as a heart failure biomarker indicate its potential contribution to post-MI matrix remodeling. Consequently, we focused on CCN1 as a potential regulator of collagen organization. Hypothesis: CCN1 guides collagen alignment to support scar integrity via enhancing fibroblast-matrix interactions. Methods & Results: Tamoxifen (TAM)-inducible Ccn1 fibroblast-specific KO ( Ccn1 -/- ) and control ( Ccn1 fl/fl ) mice (16-20 wk old) received TAM 3 wk prior to permanent coronary artery ligation. Cardiac function, heart mass, and scar structure were evaluated 1 wk post-MI using echocardiography, gravimetrics, and imaging techniques (picrosirius red, second harmonic generation, and transmission electron microscopy). Ccn1 -/- mice exhibited decreased survival (A) and an increased incidence of cardiac rupture compared to Ccn1 fl/fl (B-C). There were no differences in cardiac function or scar size among the groups. Macro- (E-F) and micro- (G) level structural analyses uncovered significant reductions in collagen organization in Ccn1 -/- mice. RNAi-mediated CCN1 depletion in fibroblasts resulted in reduced focal adhesion (FA) formation in culture (43.0 FA/cell ± 5.6 vs. 89.3 FA/cell ± 9.6; Mean ± SEM, p=0.0013, n=7), highlighting its role in facilitating fibroblast-ECM interactions. Conclusions: CCN1 is required for post-MI scar integrity. CCN1 may regulate fibroblast-ECM interactions to alter collagen organization.