Meirols A-C: Bioactive Catecholic Compounds from the Marine-Derived Fungus Meira sp. 1210CH-42.

Three new catecholic compounds, named meirols A-C (2-4), and one known analog, argovin (1), were isolated from the marine-derived fungus Meira sp. 1210CH-42. Their structures were determined by extensive analysis of 1D, 2D NMR, and HR-ESIMS spectroscopic data. Their absolute configurations were elucidated based on ECD calculations. All the compounds exhibited strong antioxidant capabilities with EC50 values ranging from 6.01 to 7.47 µM (ascorbic acid, EC50 = 7.81 µM), as demonstrated by DPPH radical scavenging activity assays. In the α-glucosidase inhibition assay, 1 and 2 showed potent in vitro inhibitory activity with IC50 values of 184.50 and 199.70 µM, respectively (acarbose, IC50 = 301.93 µM). Although none of the isolated compounds exhibited cytotoxicity against one normal and six solid cancer cell lines, 1 exhibited moderate cytotoxicity against the NALM6 and RPMI-8402 blood cancer cell lines with GI50 values of 9.48 and 21.00 µM, respectively. Compound 2 also demonstrated weak cytotoxicity against the NALM6 blood cancer cell line with a GI50 value of 29.40 µM.

Is living alone beneficial to older adults during the COVID-19 pandemic? Examining associations between living arrangements and life satisfaction by gender in Korea.

OBJECTIVES: This study examines associations between living arrangements and life satisfaction and the associated effects of gender among Korean older adults during the pandemic. METHOD: Data were drawn from the 2020 National Survey of Older Koreans-a nationally representative survey. Living arrangements were categorized into four groups: living alone; living with spouse only; living with family and spouse; and living with family without spouse. Logistic regression analyses were used to examine associations between living arrangements and life satisfaction measured as a binary outcome. RESULTS: Older adults living alone were more likely to be satisfied with life compared with those who lived with a spouse only. However, living alone became nonsignificant after controlling for social contact with friends or neighbors and social participation. Interestingly, there was a significant interaction between living arrangements and gender, showing that living alone was beneficial to older women but not to men. Subsample analysis by gender confirmed that older women living alone had a greater likelihood of being satisfied with life than those living with a spouse only, whereas men living alone had lower life satisfaction. CONCLUSION: Findings suggest that living alone is not always deleterious to older adults, particularly women. During the pandemic, older Korean women living with their spouse and/or family might be less satisfied with life due to the dual burden of family care and housework, associated with traditional gendered norms and social context.

Labdane-Type Diterpenoids from Streptomyces griseorubens and Their Antimicrobial and Cytotoxic Activities.

Chemical investigation of the ethyl acetate (EtOAc) extract from a marine-derived actinomycete, Streptomyces griseorubens, resulted in the discovery of five new labdane-type diterpenoids: chlorolabdans A-C (1-3), epoxylabdans A and B (4 and 5), along with one known analog (6). The structures of the new compounds were determined by spectroscopic analysis (HR-ESIMS, 1D, and 2D NMR) and by comparing their experimental data with those in the literature. The new compounds were evaluated for their antimicrobial activity, and 2 displayed significant activity against Gram-positive bacteria, with minimum inhibitory concentration (MIC) values ranging from 4 to 8 µg/mL. Additionally, 1, 2, and 4 were tested for their cytotoxicity against seven blood cancer cell lines by CellTiter-Glo (CTG) assay and six solid cancer cell lines by sulforhodamine B (SRB) assay; 1, 2, and 4 exhibited cytotoxic activities against some blood cancer cell lines, with concentration causing 50% cell growth inhibition (IC50) values ranging from 1.2 to 22.5 µM.

Thiolactones and Δ8,9-Pregnene Steroids from the Marine-Derived Fungus Meira sp. 1210CH-42 and Their α-Glucosidase Inhibitory Activity.

The fungal genus Meira was first reported in 2003 and has mostly been found on land. This is the first report of second metabolites from the marine-derived yeast-like fungus Meira sp. One new thiolactone (1), along with one revised thiolactone (2), two new Δ8,9-steroids (4, 5), and one known Δ8,9-steroid (3), were isolated from the Meira sp. 1210CH-42. Their structures were elucidated based on the comprehensive spectroscopic data analysis of 1D, 2D NMR, HR-ESIMS, ECD calculations, and the pyridine-induced deshielding effect. The structure of 5 was confirmed by oxidation of 4 to semisynthetic 5. In the α-glucosidase inhibition assay, compounds 2-4 showed potent in vitro inhibitory activity with IC50 values of 148.4, 279.7, and 86.0 µM, respectively. Compounds 2-4 exhibited superior activity as compared to acarbose (IC50 = 418.9 µM).

Streptinone, a New Indanone Derivative from a Marine-Derived Streptomyces massiliensis, Inhibits Particulate Matter-Induced Inflammation.

Inflammatory diseases caused by air pollution, especially from particulate matter (PM) exposure, have increased daily. Accordingly, attention to treatment or prevention for these inflammatory diseases has grown. Natural products have been recognized as promising sources of cures and prevention for not only inflammatory but also diverse illnesses. As part of our ongoing study to discover bioactive compounds from marine microorganisms, we isolated streptinone, a new indanone derivative (1), along with three known diketopiperazines (2-4) and piericidin A (5), from a marine sediment-derived Streptomyces massiliensis by chromatographic methods. The structure of 1 was elucidated based on the spectroscopic data analysis. The relative and absolute configurations of 1 were determined by 1H-1H coupling constants, 1D NOESY, and ECD calculation. The anti-inflammatory activities of 1 were evaluated through enzyme-linked immunosorbent assay (ELISA), Western blot, and qPCR. Compound 1 suppressed the production of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ß, by inhibiting the Toll-like receptor (TLR)-mediated nuclear factor kappa B (NF-κB) signaling pathway. Therefore, compound 1 could potentially be used as an agent in the prevention and treatment of diverse inflammatory disorders caused by particulate matter.

Digital technology use and depressive symptoms among older adults in Korea: beneficial for those who have fewer social interactions?

OBJECTIVES: Our study examines the relationship between digital technology use and depressive symptoms among older Koreans and whether social interaction moderates the relationship. METHODS: The data were drawn from the 2017 Survey of Living Conditions and Welfare Needs of Korean Older Persons, a nationally representative survey. Digital technology use was measured by the number of digital functions that respondents perform with their electronic devices. Social interactions were measured by the frequencies of face-to-face and remote connections with friends or neighbors. Relationships were estimated with multiple regression analyses. RESULTS: Digital technology use was inversely associated with depressive symptoms even after adjusting for covariates including cognitive function. Both remote and face-to-face connections with friends or neighbors were associated with fewer depressive symptoms. An interaction between digital technology use and remote contact also was detected: the effect of digital technology use on depressive symptoms was more beneficial for older adults with infrequent remote contact with friends or neighbors than for those with frequent remote contact. CONCLUSION: Findings suggest that digital technology use can reduce depressive symptoms of older adults, especially those who have fewer social interactions. Educating older adults to increase their digital literacy level and use of remote interactions may improve their psychological wellbeing, perhaps even during times of a viral pandemic.

The matricellular protein CCN5 prevents adverse atrial structural and electrical remodelling.

Atrial structural remodelling including atrial hypertrophy and fibrosis is a key mediator of atrial fibrillation (AF). We previously demonstrated that the matricellular protein CCN5 elicits anti-fibrotic and anti-hypertrophic effects in left ventricles under pressure overload. We here determined the utility of CCN5 in ameliorating adverse atrial remodelling and arrhythmias in a murine model of angiotensin II (AngII) infusion. Advanced atrial structural remodelling was induced by AngII infusion in control mice and mice overexpressing CCN5 either through transgenesis (CCN5 Tg) or AAV9-mediated gene transfer (AAV9-CCN5). The mRNA levels of pro-fibrotic and pro-inflammatory genes were markedly up-regulated by AngII infusion, which was significantly normalized by CCN5 overexpression. In vitro studies in isolated atrial fibroblasts demonstrated a marked reduction in AngII-induced fibroblast trans-differentiation in CCN5-treated atria. Moreover, while AngII increased the expression of phosphorylated CaMKII and ryanodine receptor 2 levels in HL-1 cells, these molecular features of AF were prevented by CCN5. Electrophysiological studies in ex vivo perfused hearts revealed a blunted susceptibility of the AAV9-CCN5-treated hearts to rapid atrial pacing-induced arrhythmias and concomitant reversal in AngII-induced atrial action potential prolongation. These data demonstrate the utility of a gene transfer approach targeting CCN5 for reversal of adverse atrial structural and electrophysiological remodelling.

Age Discrimination and Suicidal Ideation Among Korean Older Adults.

OBJECTIVE: We examined the role of age discrimination in suicidal ideation among community-dwelling older adults in South Korea. METHODS: We analyzed adults aged 65 or older residing in Korea drawn from the 2014 Survey of Living Conditions and Welfare Needs of Korean Older Persons (total unweighted n = 10,279; total weighted N = 6,280,588). Data were analyzed using chi-square, t tests, and logistic regression analyses. RESULTS: Results from logistic regression analysis showed that after adjusting for covariates, Korean elders who experienced age discrimination had 2.26 times higher odds of having suicidal ideation than those who did not. CONCLUSIONS: The experience of age discrimination increased the risk of suicidal ideation among Korean elders. Identifying ways to reduce age discrimination may be an effective means of reducing suicidal ideation, which would, in turn, potentially decrease suicide rates among older adults. There may be cross-cultural clinical implications and variations due to belief systems surrounding respect for older adults.

Role of the PRC2-Six1-miR-25 signaling axis in heart failure.

The reduced expression of cardiac sarco-endoplasmic reticulum Ca2+ ATPase (SERCA2a) is a hallmark of heart failure. We previously showed that miR-25 is a crucial transcriptional regulator of SERCA2a in the heart. However, the precise mechanism of cardiac miR-25 regulation is largely unknown. Literatures suggested that miR-25 is regulated by the transcriptional co-factor, sine oculis homeobox homolog 1 (Six1), which in turn is epigenetically regulated by polycomb repressive complex 2 (PRC 2) in cardiac progenitor cells. Therefore, we aimed to investigate whether Six1 and PRC2 are indeed involved in the regulation of the miR-25 level in the setting of heart failure. Six1 was up-regulated in the failing hearts of humans and mice. Overexpression of Six1 led to adverse cardiac remodeling, whereas knock-down of Six1 attenuated pressure overload-induced cardiac dysfunction. The adverse effects of Six1 were ameliorated by knock-down of miR-25. The epigenetic repression on the Six1 promoter by PRC2 was significantly reduced in failing hearts. Epigenetic repression of Six1 is relieved through a reduction of PRC2 activity in heart failure. Six1 up-regulates miR-25, which is followed by reduction of cardiac SERCA2a expression. Collectively, these data showed that the PRC2-Six1-miR-25 signaling axis is involved in heart failure. Our finding introduces new insight into potential treatments of heart failure.

Effect of methotrexate discontinuation on efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial.

OBJECTIVE: To investigate whether temporary discontinuation of methotrexate (MTX) improves the efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis (RA). METHODS: In this prospective randomised parallel-group trial, patients with RA taking stable dose of MTX were randomly assigned at a ratio of 1:1:1:1 to continue MTX (group 1), suspend MTX for 4 weeks before vaccination (group 2), suspend MTX for 2 weeks before and 2 weeks after vaccination (group 3) or suspend MTX for 4 weeks after vaccination (group 4). All participants were vaccinated with trivalent influenza vaccine containing H1N1, H3N2 and B-Yamagata. The primary outcome was frequency of satisfactory vaccine response (≥4-fold titre increase 4 weeks postvaccination). Secondary endpoints included fold change in antibody titres from baseline. RESULTS: The per-protocol population consisted of 199 patients (n=54, 44, 49 and 52 in groups 1, 2, 3 and 4, respectively). Group 3 achieved higher satisfactory vaccine response against all three antigens than group 1 (51.0% vs 31.5%, p=0.044). The anti-H3N2 antibody fold increase (95% CI) was significantly higher in groups 3 and 4 (12.2 (8.4 to 17.5), p <0.001 and 10.0 (6.8 to 14.8), p=0.043, respectively) than group 1 (5.9 (4.3 to 8.1)). The anti-B-Yamagata antibody responses of groups 3 and 4 were higher (4.7 (3.3 to 6.7), p=0.048; 6.1 (4.2 to 8.8), p <0.001, respectively) than group 1 (2.9 (2.2 to 3.8)). RA flare occurred in 24.1%, 21.2%, 34.1% and 38.8% in groups 1, 2, 3 and 4, respectively (p=NS). CONCLUSIONS: Temporary MTX discontinuation improves the immunogenicity of seasonal influenza vaccination in patients with RA. TRIAL REGISTRATION: Trial registration number is: www.clinicaltrials.gov, NCT02748785.

The company you keep: Is socialising with higher-status people bad for mental health?

Socialising with higher-status individuals can be hypothesised to exert opposing influences on the mental health of the ego. On the one hand, socialising with higher-status alters might enable individuals to access valuable resources. On the other hand, status-discrepant friendships could be detrimental to mental health by engendering feelings of unfairness. We sought to examine the impact of status-discrepant social relationships on depressive symptoms in the 2012 Korean General Social Survey (KGSS), a nationally representative sample. We show that socialising with higher-status people is positively associated with depressive symptoms. There is no significant difference between those socialising with equivalent-status or with lower-status alters. Perceived unfairness also increase depressive symptoms. Respondents socialising with higher-status alters tend to report greater depressive symptoms as their perceived unfairness increases. Gender-stratified analyses reveal that the detrimental impact of status-discrepant relationships are observed for men only, not for women. These findings suggest that socialising with higher-status people can be a net detriment for mental wellbeing by increasing stress/frustration or decreasing psychological resources such as self-esteem, and that these effects are more pronounced for individuals who perceive that society is unfair. This pattern appears stronger for men, which might be associated with gender roles internalised through gender socialisation processes.

Evaluation and selection of reference genes for ecotoxicogenomic study of the green alga Closterium ehrenbergii using quantitative real-time PCR.

The green alga Closterium ehrenbergii occurs in fresh water environments and has been suggested as a model for ecotoxicological assessment. Quantitative real-time PCR (qRT-PCR), with its high sensitivity and specificity, is a preferred method for reliable quantification of gene expression levels. qRT-PCR requires reference genes to normalize the transcription level of the target gene, and selection of appropriate references is crucial. Here, we evaluated nine housekeeping genes, that is, 18S rRNA, ACT, TUA, TUB, eIF, H4, UBQ, rps4, and GAPDH, using 34 RNA samples of C. ehrenbergii cultured in various environments (e.g. exposure to heat shock, UV, metals, and non-metallic chemicals). Each housekeeping gene tested displayed different ranges of C T values for each experimental condition. The gene stability was determined using the descriptive statistic software geNorm, which showed that ACT, H4, and TUA were the most suitable reference genes for all the conditions tested. In addition, at least three genes were required for proper normalization. With these references, we assessed the expression level of the heat shock protein 70 (HSP70) gene in C. ehrenbergii cells exposed to thermal and toxic contaminant stress and found that it was significantly up-regulated by these stressors. This study provides potential reference genes for gene expression studies on C. ehrenbergii with qRT-PCR.

Violapyrones H and I, new cytotoxic compounds isolated from Streptomyces sp. associated with the marine starfish Acanthaster planci.

Two new α-pyrone derivatives, violapyrones H (1) and I (2), along with known violapyrones B (3) and C (4) were isolated from the fermentation broth of a marine actinomycete Streptomyces sp. The strain was derived from a crown-of-thorns starfish, Acanthaster planci, collected from Chuuk, Federated States of Micronesia. The structures of violapyrones were elucidated by the analysis of 1D and 2D NMR and HR-ESIMS data. Violapyrones (1-4) exhibited cytotoxicity against 10 human cancer cell lines with GI50 values of 1.10-26.12 µg/mL when tested using sulforhodamine B (SRB) assay. This is the first report on the cytotoxicity of violapyrones against cancer cell lines and the absolute configuration of violapyrone C.

Gageostatins A-C, antimicrobial linear lipopeptides from a marine Bacillus subtilis.

Concerning the requirements of effective drug candidates to combat against high rising multidrug resistant pathogens, we isolated three new linear lipopeptides, gageostatins A-C (1-3), consisting of hepta-peptides and new 3-ß-hydroxy fatty acids from the fermentation broth of a marine-derived bacterium Bacillus subtilis. Their structures were elucidated by analyzing a combination of extensive 1D, 2D NMR spectroscopic data and high resolution ESIMS data. Fatty acids, namely 3-ß-hydroxy-11-methyltridecanoic and 3-ß-hydroxy-9,11-dimethyltridecanoic acids were characterized in lipopeptides 1 and 2, respectively, whereas an unsaturated fatty acid (E)-7,9-dimethylundec-2-enoic acid was assigned in 3. The 3R configuration of the stereocenter of 3-ß-hydroxy fatty acids in 1 and 2 was established by Mosher's MTPA method. The absolute stereochemistry of amino acid residues in 1-3 was ascertained by acid hydrolysis followed by Marfey's derivatization studies. Gageostatins 1-3 exhibited good antifungal activities with MICs values of 4-32 µg/mL when tested against pathogenic fungi (R. solani, B. cinerea and C. acutatum) and moderate antibacterial activity against bacteria (B. subtilis, S. aeureus, S. typhi and P. aeruginosa) with MICs values of 8-64 µg/mL. Futhermore, gageostatins 1-3 displayed cytotoxicity against six human cancer cell lines with GI50 values of 4.6-19.6 µg/mL. It is also noteworthy that mixed compounds 1+2 displayed better antifungal and cytotoxic activities than individuals.

Different transcriptional responses of heat shock protein 20 in the marine diatom Ditylum brightwellii exposed to metals and endocrine-disrupting chemicals.

Diatoms are sensitive indicators of water quality, and hence used for environmental hazard assessments; however, their toxicogenomic studies have been insufficiently attempted. In the present study, we determined the cDNA sequence of heat shock protein 20 (Hsp20) gene from the diatom Ditylum brightwellii, and examined the transcriptional responses of the gene after exposing it to environmental stressors such as thermal shock, metals, and endocrine-disrupting chemicals (EDCs). The open reading frame (ORF) of DbHsp20 was 531 bp long, encoding 177 amino acid residues (19.49 kDa) with a conserved C-terminal and α-crystallin domain. The genomic region of DbHsp20 did not contain introns. Phylogeny of eukaryotic Hsp20s showed D. brightwellii was closely related to other diatoms. With regard to the gene expressional profile, real-time PCR results showed that the gene was significantly upregulated (P < 0.001) under thermal stress, with the highest change of 3.2-fold. Metals' (copper and nickel) treatments showed that it was induced after a certain point of treated concentration. On the contrary, EDCs did not display noticeable change on the expression of DbHsp20. These results suggest that the diatom Hsp20 basically responds to thermal stress, but may differentially respond to toxic substances such as metals and organic compounds such as EDCs.

Double jeopardy: Exploring the moderating effect of educational mismatch in the relationship between work-family conflict and depressive symptoms among Korean working women.

RATIONALE: Despite a growing body of empirical evidence on the detrimental effects of work-family conflict (WFC) on psychological health, little attention has been given to whether educational mismatch in the workplace, which refers to the perceived level of match between one's attained education and the required educational level for a position, may exacerbate these effects. OBJECTIVE: The purpose of this study was to examine the relationship between WFC, educational mismatch, and depressive symptoms in Korean working women, with a particular focus on the potential moderating effects of educational mismatch on the association between WFC and depressive symptoms. METHODS: The data utilized for this study were collected from 5174 married working women over five waves (16,610 person-observations) of the Korean Longitudinal Survey of Women and Families spanning 8 years between 2012 and 2020. Fixed effects (FE) models were estimated to account for unobserved individual-level heterogeneity. RESULTS: FE estimates indicated that WFC is associated with an increase in depressive symptoms, even after accounting for unobserved confounding factors and time-varying covariates. The interaction model provides evidence for the moderating role of educational mismatch in the association between WFC and depressive symptoms. The positive association between WFC and depressive symptoms was more pronounced among those who perceive themselves as "overeducated." The estimated coefficient for the association was about 45% larger for those who perceive themselves as "overeducated" than their "well-matched" counterparts. CONCLUSION: The study's findings suggest a robust link between WFC and depressive symptoms and further elaborate on how this association varies depending on educational mismatch. In Korea, where conservative gender role norms of female-caregiver ideology are still prevalent, WFC and educational mismatch can act as double jeopardy, exacerbating the mental health of working women.

Effect of information provision on parental intention toward COVID-19 vaccination for children: a nationwide survey experiment.

The reluctance of parents to vaccinate their children against COVID-19 was prevalent particularly when uncertainty over vaccination outcomes prevailed. We conducted a nationwide randomized online survey experiment to assess the effect of information provision on parental intention for COVID-19 vaccination before the government started vaccination for children in South Korea. Parents of elementary school children were provided with either no information (Control), information on vaccine profile (vaccine informed group; VI), or COVID-19 (disease informed group; DI). Among 359,110 participants, parental intention for vaccination of children was significantly higher in both VI and DI groups compared with the Control group. In terms of effect size, information on COVID-19 vaccine increased likelihood to vaccinate by 1620 per 100,000 parents and reduced vaccine hesitancy by 1340 per 100,000 parents. Consistently with the positive effect on vaccination intention, both VI and DI interventions increased participants' perceptions on vaccination benefits being higher than its risks and vaccination risks being lower than health risks of COVID-19 infection, and self-reported trust in COVID-19 information. Our results lend strong support to the claim that the provision of targeted, tailored information on COVID-19 vaccine and infection increases parental intention to vaccinate children and reduces vaccine hesitancy.

Does having children matter? Associations between transitions in work-family role combinations and depressive symptoms among married women in Korea.

Although having a variety of roles is generally beneficial for mental health, little is known about the relationships between work-family role combinations and depressive symptoms among married women in Korea, where child rearing is strongly considered a mother's responsibility. This study examines how the four types of work-family role combinations may be associated with depressive symptoms among married Korean women younger than 50 years old. Data were collected from 2012 through 2020 in five surveys by the Korean Longitudinal Survey of Women & Families. In total, 4811 married women (14,851 person-period observations) were analyzed using regression models with fixed effects. This enabled estimation of the within-person effects of transitions in work-family role combinations on depressive symptoms. Work-family role combinations were categorized as follows based on whether respondents had a job or at least one child: having both worker and mother roles, having a worker role only, having neither a worker nor a mother role, and having a mother role only. The findings indicate that married women who had only a mother role had more severe depressive symptoms than the other three groups. However, after controlling for whether respondents had a preschool-aged child, only those with both worker and mother roles had significantly lower levels of depressive symptoms compared with those with a mother role only. This study suggests that transitioning to being a working mother from a full-time mother may benefit the mental health of married Korean women. Furthermore, whether married women have a child critically impacts their mental health more than the number of roles. Raising a preschool-aged child seems to potentially be especially stressful for married Korean women. Working outside the home can protect the mental health of married Korean mothers who are affected by the social pressure to immerse themselves in child-rearing.

I Am Not Supposed to Be Treated Like This: Associations Between Age Discrimination, Perceived Social Respect for Older Adults, and Depressive Symptoms in Korean Older Adults.

OBJECTIVES: This study examines the relationships between age discrimination, perceived social respect for older adults as a proxy of perceived social climate, and depressive symptoms in older adults in Korea. In doing so, it clarifies whether and how age discrimination has a differential effect on mental health, depending on the level of perceived social respect. METHODS: This study uses multiple regression analyses to examine the data obtained from the 2020 National Survey of Older Koreans, a nationally representative survey. RESULTS: Findings show that age discrimination was positively associated with depressive symptoms, whereas perceived social respect for older adults was negatively associated with depressive symptoms. Older respondents exhibited fewer depressive symptoms if they felt that older adults were respected in Korea. The results also revealed a significant interaction between age discrimination and perceived social respect; age discrimination had a more harmful impact on depressive symptoms in older adults with a higher level of perceived social respect. DISCUSSION: The findings suggest that a positive social climate for older adults is beneficial to their mental health, but ironically, it may form a more stressful context for older adults who experience age discrimination that is characteristically opposite from their subjective evaluation of that social climate. The gap between the expected social climate and individual discriminatory experiences may have a deleterious effect on the mental health of older adults.

The matricellular protein CCN5 induces apoptosis in myofibroblasts through SMAD7-mediated inhibition of NFκB.

We previously showed that the matricellular protein CCN5 reverses established cardiac fibrosis (CF) through inducing apoptosis in myofibroblasts (MyoFBs) but not in cardiomyocytes or fibroblasts (FBs). In this study, we set out to elucidate the molecular mechanisms underlying CCN5-mediated selective apoptosis of MyoFBs. We first observed that the apoptotic protein p53 and the anti-apoptotic protein NFκB are simultaneously induced in MyoFBs. When the expression level of p53 was suppressed using a siRNA, CCN5 did not induce apoptosis in MyoFBs. By contrast, when NFκB signaling was inhibited using IKK VII, an IκB inhibitor, MyoFBs underwent apoptosis even in the absence of CCN5. SMAD7 is one of the downstream targets of CCN5 and it was previously shown to potentiate apoptosis in epithelial cells through inhibition of NFκB. In accordance with these reports, when the expression of SMAD7 was suppressed using a siRNA, NFκB signaling was enhanced, and CCN5 did not induce apoptosis. Lastly, we used a luciferase reporter construct to show that CCN5 positively regulated SMAD7 expression at the transcriptional level. Collectively, our data suggest that a delicate balance between the two mutually antagonistic proteins p53 and NFκB is maintained for MyoFBs to survive, and CCN5 tips the balance in favor of the apoptotic protein p53. This study provides insight into the anti-fibrotic activity of CCN5 during the regression of CF.