RESUMO
Podocyte dysfunction plays a crucial role in renal injury and is identified as a key contributor to proteinuria in Fabry disease (FD), primarily impacting glomerular filtration function (GFF). The α3ß1 integrins are important for podocyte adhesion to the glomerular basement membrane, and disturbances in these integrins can lead to podocyte injury. Therefore, this study aimed to assess the effects of chloroquine (CQ) on podocytes, as this drug can be used to obtain an in vitro condition analogous to the FD. Murine podocytes were employed in our experiments. The results revealed a dose-dependent reduction in cell viability. CQ at a sub-lethal concentration (1.0 µg/mL) induced lysosomal accumulation significantly (p < 0.0001). Morphological changes were evident through scanning electron microscopy and immunofluorescence, highlighting alterations in F-actin and nucleus morphology. No significant changes were observed in the gene expression of α3ß1 integrins via RT-qPCR. Protein expression of α3 integrin was evaluated with Western Blotting and immunofluorescence, demonstrating its lower detection in podocytes exposed to CQ. Our findings propose a novel in vitro model for exploring secondary Fabry nephropathy, indicating a modulation of α3ß1 integrin and morphological alterations in podocytes under the influence of CQ.
Assuntos
Doença de Fabry , Integrina alfa3beta1 , Nefropatias , Podócitos , Animais , Camundongos , Doença de Fabry/metabolismo , Integrina alfa3beta1/genética , Integrina alfa3beta1/metabolismo , Nefropatias/metabolismo , Podócitos/metabolismo , Insuficiência RenalRESUMO
The aim of the present study was to compare the expression of α2ß1, α3ß1, and α5ß1 integrins between 28 pleomorphic adenomas (PAs) and 10 adenoid cystic carcinomas (ACCs), and investigate differences in the expression of these integrins according to histologic subtypes of ACCs. It was taken into consideration the presence or absence, distribution, and localization of integrin immunoexpression. There was immunoreactivity in the intercellular contacts of the strands, nests, and solid sheets of PAs, as well as in the luminal and nonluminal cells of the duct-like structures, with a predominant immunoexpression in the luminal cells. The immunoexpression in ACCs varied with histologic subtype of the tumor. It was verified for a tendency of absence and/or reduced expression of all integrins in the solid subtype of ACCs. In general, PAs revealed a more diffuse and remarkable immunoexpression of all studied integrins than ACCs. The reduced integrins expression in ACC may be related to a lesser degree of cell differentiation in this neoplasm. Moreover, the absence and/or reduced expression of the studied integrins in solid ACC suggest a possible role in pathogenesis and more aggressive biological behavior of this histologic subtype.
Assuntos
Adenoma Pleomorfo/genética , Biomarcadores Tumorais/genética , Carcinoma Adenoide Cístico/genética , Integrina alfa2beta1/genética , Integrina alfa3beta1/genética , Integrina alfa5beta1/genética , Neoplasias das Glândulas Salivares/genética , Adenoma Pleomorfo/diagnóstico , Adenoma Pleomorfo/patologia , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/patologia , Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/patologiaRESUMO
OBJECTIVE AND METHODS: This study analyzed the distribution, intensity, and pattern of immunohistochemical expression of α2ß1, α3ß1, and α5ß1 integrins in squamous cell carcinoma (SCC) of the lower lip and tongue to identify biomarkers that reflect the clinical course of this cancer. Immunoexpression was compared considering prognostic parameters such as anatomic site, metastasis, and histologic grade of malignancy. RESULTS: Immunohistochemical analysis at the invasion front showed a predominance of granular cytoplasmic expression of the integrins studied. In most cases, immunopositive cells were diffusely distributed in the tumors, irrespective of their location, except for α3ß1 integrin-positive cells which were focally distributed in 53.3% of tongue SCC cases. With respect to staining intensity, positive staining for α2ß1 integrin was observed in 80% of lower lip SCCs and in 93.3% of tongue SCCs. Staining for α3ß1 integrin was moderately positive in 60% of lower lip and tongue SCCs. The staining intensity of α5ß1 integrin was moderately and strongly positive in 53.3% and 46.7% of lower lip SCCs, respectively, and in 46.7% and 53.3% of tongue SCCs. CONCLUSIONS: The strong immunoreactivity for integrins α2ß1, α3ß1, and α5ß1 seen in the oral SCC cases studied suggests a significant participation of these proteins in oral carcinogenesis. However, their expression does not reflect the clinical course of this cancer.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Transformação Celular Neoplásica/patologia , Integrina alfa2beta1/genética , Integrina alfa3beta1/genética , Integrina alfa5beta1/genética , Neoplasias Labiais/patologia , Neoplasias da Língua/patologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Transformação Celular Neoplásica/genética , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Labiais/diagnóstico , Neoplasias Labiais/genética , Masculino , Gradação de Tumores , Neoplasias da Língua/diagnóstico , Neoplasias da Língua/genéticaRESUMO
Ameloblastoma is an odontogenic neoplasm characterized by local invasiveness and a tendency toward recurrence, whereas adenomatoid odontogenic tumor (AOT) is an indolent neoplasm. The objective of the present study was to immunohistochemically analyze the role of alpha2beta1, alpha3beta1, and alpha5beta1 integrins in the cellular events and cell-matrix interactions that occur in these tumors and their consequent repercussions on the architectural arrangement and biologic behavior of these lesions. Paraffin-embedded specimens from 30 ameloblastomas (20 solid and 10 unicystic tumors) and 12 AOTs were submitted to immunohistochemistry using the catalyzed signal amplification system. A difference in the pattern of integrin expression was observed between the various histologic types of ameloblastoma. No significant difference in labeling intensity was observed between unicystic and solid ameloblastomas, but comparison between ameloblastomas and AOT showed a significantly stronger expression of alpha5beta1 integrin in the former (P < .05). Our findings suggest an important role of the integrins studied in the architectural characteristics of ameloblastomas and AOTs and a possible participation of alpha5beta1 integrin in the mechanism of local invasion of ameloblastomas.