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Fear-of-intimacy-mediated zinc transport controls fat body cell dissociation through modulating Mmp activity in Drosophila.

ABSTRACT: Matrix metalloproteinases (Mmps) are pivotal extracellular proteinases that have been implicated in tumour invasion and metastasis. Drosophila fat body is important for energy storage and utilization, as well as biosynthetic and metabolic activities. The fat body undergoes remodelling during metamorphosis which is characterized by the dissociation of the fat body into individual cells. Mmps play important roles in the regulation of fat body cell dissociation. Here we show that a zinc transporter fear-of-intimacy (foi) is necessary for the cell dissociation of fat body in Drosophila. The progression of fat body cell dissociation was delayed by fat body-specific foi knockdown while it was accelerated by foi overexpression (OE). In essence, these phenotypes are closely associated with intracellular zinc homeostasis, which can be modulated by dietary zinc intervention or genetic modulation of other zinc transporters. Further study indicated that Mmp1 and Mmp2 levels could be transcriptionally regulated by zinc in vivo. Consistently, the retarded fat body cell dissociation caused by Mmp1 or Mmp2 RNAi could be regulated by modulating the expression of foi. Further, by using Drosophila models of malignant tumour Raf^GOFscrib^-/- and Ras^V12lgl^-/-, we showed that the tumour growth, invasion and migration could be markedly inhibited by foi knockdown. These findings demonstrate a close connection between zinc levels and cell dissociation in vivo, and also suggest that manipulation of zinc levels may provide a novel therapeutic strategy for cancer.

SUBMITTER: Wei T

PROVIDER: S-EPMC8464599 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:This study aimed to evaluate the internal consistency, reliability, convergent validity, known-group comparisons, and structural validity of the Chinese version of Fear of Intimacy with Helping Professionals (C-FIS-HP) scale in Macau.A cross-sectional design was used on a sample of 593 older people in 6 health centers. We used Chinese version of Exercise of Self-Care Agency Scale (C-ESCAS) and Morisky 4-item medication adherence scale to evaluate self-care actions and medication adherence. The internal consistency and reliability of C-FIS-HP were analyzed using the Spearman-Brown split-half reliability, Cronbach's alpha, and test-retest reliability. Convergent validity was tested the construct of C-FIS-HP and self-care actions. Known-group comparisons differentiated predefined groups in an expected direction. Two separated samples were used to test the structural validity. An exploratory factor analysis (EFA) tested the factor structure of C-FISHP using the principal axis factoring. A confirmatory factor analysis (CFA) was further conducted to confirm the factor structure constructed in the prior EFA.The C-FIS-HP had a Spearman-Brown split-half coefficient, Cronbach's alpha, and intraclass correlation coefficient of 0.96, 0.93, and 0.96, respectively. Convergent validity was satisfactory with significantly correlations between the C-FIS-HP and C-ESCAS. C-FIS-HP to differentiate the differences between high-, moderate-, and low- medication adherence groups. EFA demonstrated a two-factor structure among 297 older people. A first-order CFA was performed to confirm the construct dimensionality of C-FIS-HP with satisfactory fit indices (NFI = 0.92; IFI = 0.95; TLI = 0.94; CFI = 0.95 and RMSEA = 0.07) among 296 older people.C-FIS-HP is a reliable and valid test for assessing helping relationships in older Chinese people. Health professionals can use C-FIS-HP as a clinical tool to assess the comfort level of patients in a helping relationship, and use this information to develop culturally sensitive therapeutic interventions and treatment plans. Further studies need to be conducted concerning the different psychometric properties, as well as the application of C-FIS-HP in various regions.

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Fear-of-intimacy-mediated zinc transport controls fat body cell dissociation through modulating Mmp activity in Drosophila.

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