Disease relevance of WISP3

• RESULTS: WISP3 mRNA is expressed in synovial tissue, but is 11-fold higher in RA than osteoarthritis (OA) or normal samples [1].
• We have found that WISP3 is lost in 80% of human IBC tumors and that it has growth- and angiogenesis-inhibitory functions in breast cancer in vitro and in vivo [2].
• WNT1 inducible signaling pathway protein 3, WISP-3, a novel target gene in colorectal carcinomas with microsatellite instability [3].
• OBJECTIVE: WISP3 (Wnt-1-inducible secreted protein 3) is a member of the CCN (connective tissue growth factor, cysteine-rich 61, nephroblastoma overexpressed) family of connective tissue growth factors [4].
• Wnt-1-inducible signaling pathway protein 3 and susceptibility to juvenile idiopathic arthritis [5].

Psychiatry related information on WISP3

• METHODS: Using a telephone survey and the Edinburgh Postnatal Depression Scale questionnaire we identified PPD in a sample of women who gave birth in HaEmek Medical Center. We also assessed the extent to which the women consulted with family physicians, gynecologists and/or pediatricians [6].
• CONCLUSIONS: Although many men in the postnatal period experience a variety of mental health problems, those who have a partner with PPD are themselves at increased risk for experiencing psychological symptoms and disturbances [7].

High impact information on WISP3

• We have identified nine different WISP3 mutations in unrelated, affected individuals, indicating that the gene is essential for normal post-natal skeletal growth and cartilage homeostasis [8].
• PPD is an autosomal recessive disorder that may be initially misdiagnosed as juvenile rheumatoid arthritis [8].
• A loss of function mutation in WISP3 derived from microsatellite unstable gastric carcinoma [9].
• WNT-inducible signaling pathway protein 3, WISP-3, is mutated in microsatellite unstable gastrointestinal carcinomas but not in endometrial carcinomas [10].
• Together with a third related gene, WISP-3, these proteins define a subfamily of the connective tissue growth factor family [11].

Chemical compound and disease context of WISP3

• WISP3 and RhoC guanosine triphosphatase cooperate in the development of inflammatory breast cancer [12].
• RESULTS: All the adjuvants were effective in inhibiting the development of allergen-induced airway eosinophilia, mucous production and, with the exception of PPD, also airway hyper-reactivity, when they were applied together with OVA/alum [13].

Biological context of WISP3

• METHODS: The exons and the intron/exon boundaries of the WISP3 gene were mutation-screened by denaturing high-performance liquid chromatography in 86 patients with polyarticular-course JIA (>/=5 joints affected) and 15 controls [5].
• WISP3 is of particular interest because it contains a microsatellite region in its coding region that is susceptible to frameshift mutations and leads to a truncated protein [1].
• CONCLUSION: WISP3 gene expression is higher in RA synovium and FLS compared with OA and normal synovial tissue and is further induced by proinflammatory cytokines in vitro [1].
• Moreover, we identified two novel variants, generated by alternative splicing of WISP1 and WISP3, respectively, named WISP1 delta ex3-4 and WISP3vL [14].
• WISP-3 mapped to chromosome 6q22-6q23 and also was overexpressed (4- to >40-fold) in 63% of the colon tumors analyzed [11].

Anatomical context of WISP3

• Inhibition of CCN6 (WISP3) expression promotes neoplastic progression and enhances the effects of insulin-like growth factor-1 on breast epithelial cells [15].
• Surprisingly, WISP3 protein levels are similar in RA, OA, and normal synovium samples [1].
• RESULTS: Immunohistochemistry experiments demonstrated that WISP3 protein is expressed in the midzone chondrocytes of normal adult articular cartilage, in chondrocyte clusters of osteoarthritic cartilage, and in the zone of proliferating chondrocytes of fetal growth cartilage [4].
• Conversely, restoration of WISP3 expression in the highly malignant IBC cell line SUM149 was able to decrease the expression of RhoC protein [16].
• T cell mediated, Con A induced suppression of lymphocyte response to PPD was increased in AN-patients compared to the control group with low (1mug/ml) Con A concentration, but unchanged with high (5 mug/ml) Con A concentration [17].

Associations of WISP3 with chemical compounds

• We found concordant and consistent alterations of two genes in 90% of IBC tumors when compared with stage-matched non-IBC tumors: overexpression of RhoC guanosine triphosphatase and loss of WNT-1 induced secreted protein 3 (WISP3) [12].
• CONCLUSIONS: Taken together our data suggest that live BCG>hk-BCG>CpG-ODN >PPD are effective in suppressing allergen-induced Th2 responses [13].
• PPD and Rh2 also increased MX uptake [18].
• Most of these values are below the recommended KMnO4 treatment rate of at least 2.0 mg/L or 2.5 times the water's potassium permanganate demand (PPD; an estimation of the available reducing agents in the exposure water), suggesting significant environmental risk [19].
• In male patients, carba mix, black rubber (PPD) mix and epoxy resin sensitivity was more frequent, whereas nickel sulfate, fragrance mix, ethylenediamine dihydrochloride and cobalt chloride sensitivity was significantly more frequent in female patients [20].

Regulatory relationships of WISP3

• CONCLUSION: Our experimental results suggest that WISP3 supports cartilage integrity by regulating the expression of type II collagen and aggrecan, and mutations linked with PPRD can compromise this function and produce cartilage loss [4].

Other interactions of WISP3

• We hypothesized that inhibition of CCN6 might result in the loss of a growth regulatory function that protects mammary epithelial cells from the tumorigenic effects of growth factors, particularly IGF-1 [15].
• Mutation analysis in the coding region microsatellite of the WISP3 gene in RA and OA synovium and FLS shows a limited number of insertion and deletion mutations [1].
• RESULTS: Antisense inhibition of WISP3 in HME cells increased RhoC mRNA levels and resulted in an increase in cellular proliferation, anchorage-independent growth and VEGF levels in the conditioned medium [12].
• WISP3-dependent regulation of type II collagen and aggrecan production in chondrocytes [4].
• Together, our results lead to a new hypothesis that Snail and ZEB1 are downstream of CCN6 and play a critical role in CCN6-mediated regulation of E-cadherin in breast cancer [21].

Analytical, diagnostic and therapeutic context of WISP3

• Immunohistochemistry of synovial tissue reveals that WISP3 protein is located primarily in the synovial intimal lining [1].
• METHODS: mRNA and protein expression of WISP3 were determined by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis, respectively [1].
• Alterations in WISP3-mediated messenger RNA and protein expression of cartilage-specific molecules were assessed by reverse transcriptase-polymerase chain reaction and immunoblotting [4].
• Interferon-gamma (IFN-gamma) response to M. tuberculosis purified protein derivative (M.tb PPD) in a 6-day whole blood assay and delayed type hypersensitivity (DTH) to tuberculin PPD were determined before and 1 year after receiving BCG or no vaccination [22].
• A one-stage tuberculin skin test (TST) was performed using two units of PPD RT23 [23].

References