Search

Objective: Integrins exert regulatory functions in placentogenesis. Null mutation of certain integrin α subunits leads to placental defects with subsequent fetal growth restriction or embryonic lethality in mice. So far, the placental role of α8 integrin remains to be determined. Methods: Localization of α8 integrin and its ligands, fibronectin (FN) and osteopontin (OPN), was studied by immunohistochemistry in human, rat, and mouse placenta. The vascularization of the placental labyrinth layer of α8 integrin-deficient mice was determined by CD31 staining. In humans, α8 integrin expression was assessed via real-time polymerase chain reaction in healthy placentas, in the placental pathologies such as intrauterine growth restriction (IUGR), preeclampsia, and HELLP-syndrome (hemolysis, elevated liver enzymes, low platelet count), as well as in primary extravillous trophoblasts (EVT) and villous trophoblasts. Results: In humans, α8 integrin was detected in first and third trimester syncytiotrophoblast and EVT. Although OPN showed the same localization, FN was observed in EVT only. No expressional changes in α8 integrin were detected in the placental pathologies studied. Rodent placenta showed α8 integrin expression in giant cells and in the labyrinth layer. The localization of OPN and FN, however, showed species-specific differences. Knockout of α8 integrin in mice did not cause IUGR, despite some reduction in labyrinth layer vascularization. Conclusion: α8 Integrin is expressed in functional placental compartments among its ligands, OPN and/or FN, across species. Although this may point to a regulatory role in trophoblast function, our data from α8 integrin-deficient mice indicated only mild placental pathology. Thus, the lack of placental α8 integrin seems to be largely compensated for. [ABSTRACT FROM AUTHOR]

Integrins play an important role in cancer growth and metastasis. This study aimed at determining the predictive ability of integrins and associated genes identified through molecular network in clear cell renal cell carcinoma. A total of 525 patients with ccRCC from The Cancer Genome Atlas (TCGA) cohorts were collected in this study. The expression profile of integrins and related genes were obtained from the TCGA RNAseq database. Clinicopathological characteristics, including age, gender, tumor size, tumor node metastasis (TNM), tumor grade, stage, laterality, and overall survival were collected. Cox proportional hazards regression model as well as Kaplan-Meier curve were used to assess the relative factors. Genes of integrin family that showed certain correlations with overall survival (OS) were further validated in the Fudan University Shanghai Cancer Center (FUSCC) cohort. In the TCGA cohort, after Cox proportional hazards analysis, ITGA2B (hazards ratio (HR) = 1.232, 95 % CI 1.097 to 1.383) and ITGA8 (HR = 0.804, 95 % CI 0.696 to 0.930) were shown predictive of ccRCC prognosis. Low ITGA8 expression was associated with poor prognosis for OS (log-rank test, p < 0.0001), while high level of ITGA2B expression was correlated with poor prognosis for OS (log-rank test, p < 0.0001). This finding was validated in FUSCC cohort (log-rank test, all p < 0.05). As a result, low ITGA8 expression was associated with poor prognosis for OS (log-rank test, p = 0.0053), while high level of ITGA2B expression was correlated with poor prognosis for OS (log-rank test, p < 0.0001). Plus, low ITGA8 expression was associated with poor prognosis for disease-free survival (DFS) in the TCGA cohort (log-rank test, p < 0.0001). In the gene cluster network analysis, GIT1 and SHC1 associated with ITGA2B and ITGA8 were identified as independent predictive factors of overall survival of ccRCC. ITGA2B, ITGA8, GIT1, and SHC1 were identified as independent prognostic factors of overall survival of ccRCC. This method may act as a tool to reveal more prognostic-associated genes in ccRCC. [ABSTRACT FROM AUTHOR]

Glomerulonephritis results in a dysregulation of glomerular cells and may end up in chronic alterations and subsequent loss of renal function. Therefore, understanding mechanisms, which contribute to maintain glomerular integrity, is a pivotal prerequisite for therapeutic interventions. The alpha-8 integrin chain seems to be an important player to maintain glomerular homeostasis by conferring mechanical stability and functional support for the renal capillary tuft. [ABSTRACT FROM AUTHOR]