RESUMO
Plants have a variety of regulatory mechanisms to perceive, transduce, and respond to biotic and abiotic stress. One such mechanism is the calcium-sensing CBL-CIPK system responsible for the sensing of specific stressors, such as drought or pathogens. CBLs perceive and bind Calcium (Ca2+) in response to stress and then interact with CIPKs to form an activated complex. This leads to the phosphorylation of downstream targets, including transporters and ion channels, and modulates transcription factor levels and the consequent levels of stress-associated genes. This review describes the mechanisms underlying the response of the CBL-CIPK pathway to biotic and abiotic stresses, including regulating ion transport channels, coordinating plant hormone signal transduction, and pathways related to ROS signaling. Investigation of the function of the CBL-CIPK pathway is important for understanding plant stress tolerance and provides a promising avenue for molecular breeding.
Assuntos
Proteínas de Plantas , Transdução de Sinais , Estresse Fisiológico , Estresse Fisiológico/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Plantas/genética , Plantas/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Cálcio/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
The transforming growth factor beta (TGF-beta) is a vital regulator of placental development and functions. TGF-beta exerts several modulatory effects on trophoblast cells, such as inhibition of proliferation and invasiveness, and stimulation of differentiation by inducing multinucleated cell formation. In this study, we determine the expression patterns of TGF-beta signaling molecules in normal trophoblast, various hydatidiform mole types and choriocarcinoma. A total of 132 cases, including 51 normal placenta (20 first trimester, 11 second trimester, and 20 third trimester) and 81 gestational trophoblastic diseases (17 choriocarcinoma, and 64 hydatidiform moles: 39 complete, 6 partial, and 19 invasive) were immunohistochemically analyzed with anti-TGF beta1/2, TGF-beta receptor type I (TbetaRI), TbetaRII, Smad 2/3, and Smad 4 antibodies on paraffin blocks. In the case of normal placenta, maximal levels of all TGF-beta signaling molecules were observed in villous trophoblast in the first trimester, which decreased with gestational age. Expression of all the TGF-beta signaling proteins except Smad2/3, was significantly enhanced in various moles, relative to normal trophoblast. Moreover, TGF-beta signaling molecules were significantly downregulated in choriocarcinoma, compared to moles. In particular, TbetaRI and Smad2/3 levels were lower in choriocarcinoma than normal villous trophoblast (TbetaRI: p<0.025, Smad2/3: p<0.001). In conclusion, the TGF-beta signaling pathway plays an important role in the pathogenesis and progression of gestational trophoblastic disease, and may thus be employed as a potential therapeutic target and a diagnostic biomarker.
Assuntos
Coriocarcinoma/metabolismo , Mola Hidatiforme/metabolismo , Placenta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta2/metabolismo , Neoplasias Uterinas/metabolismo , Receptores de Ativinas Tipo I/metabolismo , Adulto , Biomarcadores Tumorais/metabolismo , Coriocarcinoma/patologia , Feminino , Idade Gestacional , Humanos , Mola Hidatiforme/patologia , Técnicas Imunoenzimáticas , Placenta/patologia , Gravidez , Proteínas Serina-Treonina Quinases , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Proteínas Smad/metabolismo , Análise Serial de Tecidos , Neoplasias Uterinas/patologiaRESUMO
Gallbladder carcinomas are rare but highly lethal neoplasms. We examined the expression of five cell-cycle-related molecules (p53, RB, cyclin D1, p27, Ki-67), and MSH2, in 46 carcinomas, 14 adenomas, 15 low-grade dysplasias, 9 intestinal metaplasias and 20 normal gallbladder epithelia. The expression of these molecules was altered in gallbladder carcinomas and adenomas. In gallbladder carcinomas we observed increased expression of p53, cyclin D1, Ki-67, and MSH2 together with decreased expression of RB and p27 protein. Aberrant expression of cyclin D1 and reduced expression of RB were noted in adenomas, and expression of cyclin D1 was elevated in low-grade dysplasias. However, there was no change in the levels of these cell-cycle molecules in metaplasia. Expression of p53, p27, Ki-67, and MSH2 was correlated with clinical stage (P<0.05) and there was also a correlation between the expression of Ki-67 and MSH-2 and patient age (P<0.05). These results suggest that altered expression of cell-cycle molecules p53, cyclin D1, RB, p27, and of MSH-2 is involved in the progression of gallbladder carcinomas.