Epithelial-mesenchymal transition (EMT) plays a crucial role in the development of cataract. This study aimed to explore the effects of TRPM7 on the proliferation and differentiation of human lens epithelial cells. TRPM7 was over-expressed in LECs treated with TGF-β2. Down-regulation of TRPM7 attenuated the increase in cell viability and cell proliferation induced by TGF-β2. The LEC migration induced by TGF-β2 was also repressed by down-regulation of TRPM7. Epithelial-specific protein E-cadherin was up-regulated through knock-down of TRPM7. EMT-specific proteins, α-SMA, fibronectin and vimentin, were down-regulated through knockdown of TRPM7. Moreover, phosphorylation of Smad2 and Smad3 was also prevented by inhibition of TRPM7. Therefore, TRPM7 elicited LEC proliferation and EMT through enhancing activation of the TGF-β/Smad pathways, implying a new therapeutic target for cataract.

• MeSH
• epitelové buňky metabolismus   MeSH
• katarakta * metabolismus   MeSH
• kationtové kanály TRPM * metabolismus   MeSH
• lidé MeSH
• proliferace buněk MeSH
• protein-serin-threoninkinasy MeSH
• signální transdukce MeSH
• transformující růstový faktor beta2 metabolismus   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: Posterior polymorphous corneal dystrophy (PPCD) is characterized by abnormal proliferation of corneal endothelial cells. It was shown that TGF-β2 present in aqueous humor (AH) could help maintaining the corneal endothelium in a G1-phase-arrest state. We wanted to determine whether the levels of this protein are changed in AH of PPCD patients. METHODS: We determined the concentrations of active TGF-β2 in the AH of 29 PPCD patients (42 samples) and 40 cadaver controls (44 samples) by ELISA. For data analysis the PPCD patients were divided based on either the molecular genetic cause of their disease as PPCD1 (37 samples), PPCD3 (1 sample) and PPCDx (not linked to a known PPCD loci, 4 samples) or on the presence (17 samples) or absence (25 samples) of secondary glaucoma or on whether they had undergone penetrating keratoplasty (PK, 32 samples) or repeated PK (rePK, 7 samples). RESULTS: The level of active TGF-β2 in the AH of all PPCD patients (mean ± SD; 386.98 ± 114.88 pg/ml) in comparison to the control group (260.95 ± 112.43 pg/ml) was significantly higher (P = 0.0001). Compared to the control group, a significantly higher level of active TGF-β2 was found in the PPCD1 (P = 0.0005) and PPCDx (P = 0.0022) groups. Among patients the levels of active TGF-β2 were not significantly affected by gender, age, secondary glaucoma or by the progression of dystrophy when one or repeated PK were performed. CONCLUSION: The levels of active TGF-β2 in the AH of PPCD patients are significantly higher than control values, and thus the increased levels of TGF-β2 could be a consequence of the PPCD phenotype and can be considered as another feature characterizing this disease.

• MeSH
• dědičné dystrofie rohovky metabolismus   MeSH
• glaukom metabolismus   MeSH
• keratoplastika perforující metody   MeSH
• komorová voda metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• rohovka metabolismus   MeSH
• rohovkový endotel metabolismus   MeSH
• transformující růstový faktor beta2 metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Metastasized malignant melanoma has a poor prognosis because of its intrinsic resistance to chemotherapy and radiotherapy. The central role in the melanoma transcriptional network has the transcription factor MITF (microphthalmia-associated transcription factor). It has been shown recently that the expression of MITF and some of its target genes require the SWI/SNF chromatin remodeling complex. Here we demonstrate that survival of melanoma cells requires functional SWI/SNF complex not only by supporting expression of MITF and its targets and but also by activating expression of prosurvival proteins not directly regulated by MITF. Microarray analysis revealed that besides the MITF-driven genes, expression of proteins like osteopontin, IGF1, TGFß2 and survivin, the factors known to be generally associated with progression of tumors and the antiapoptotic properties, were reduced in acute BRG1-depleted 501mel cells. Western blots and RT-PCR confirmed the microarray findings. These proteins have been verified to be expressed independently of MITF, because MITF depletion did not impair their expression. Because these genes are not regulated by MITF, the data suggests that loss of BRG1-based SWI/SNF complexes negatively affects survival pathways beyond the MITF cascade. Immunohistochemistry showed high expression of both BRM and BRG1 in primary melanomas. Exogenous CDK2, osteopontin, or IGF1 each alone partly relieved the block of proliferation imposed by BRG1 depletion, implicating that more factors, besides the MITF target genes, are involved in melanoma cell survival. Together these results demonstrate an essential role of SWI/SNF for the expression of MITF-dependent and MITF-independent prosurvival factors in melanoma cells and suggest that SWI/SNF may be a potential and effective target in melanoma therapy.

• MeSH
• apoptóza genetika   MeSH
• chromozomální proteiny, nehistonové genetika   metabolismus   MeSH
• cyklin-dependentní kinasa 2 genetika   metabolismus   MeSH
• DNA-helikasy genetika   metabolismus   MeSH
• imunohistochemie MeSH
• inhibitory apoptózy genetika   metabolismus   MeSH
• insulinu podobný růstový faktor I genetika   metabolismus   MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• lidé MeSH
• melanom genetika   metabolismus   patologie   MeSH
• nádorové buněčné linie MeSH
• névus genetika   metabolismus   patologie   MeSH
• osteopontin genetika   metabolismus   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proliferace buněk MeSH
• RNA interference MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• stanovení celkové genové exprese MeSH
• transformující růstový faktor beta2 genetika   metabolismus   MeSH
• transkripční faktor spojený s mikroftalmií genetika   metabolismus   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• viabilita buněk genetika   MeSH
• western blotting MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Submitted project deals with the immunosuppresive effects of glioblastoma cells caused by overexpression of transforming growth factor beta and contributes to enhancement of current cellular immunotherapy.

Předkládaný projekt se snaží překlenout imunosupresívní efekt buněk glioblastomu vyvolaný účinkem transformujícího růstového faktoru beta a umožnit tak účinně využít možnosti buněčné imunoterapie.

• MeSH
• glioblastom MeSH
• imunosupresivní léčba MeSH
• imunoterapie MeSH
• transformující růstový faktor beta2 MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• neurologie
• onkologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

• MeSH
• antigen Ki-67 metabolismus   MeSH
• barva vlasů účinky léků   MeSH
• buněčné dělení účinky léků   MeSH
• dospělí MeSH
• financování organizované MeSH
• imunohistochemie MeSH
• keratinocyty cytologie   účinky léků   MeSH
• koncové značení zlomů DNA in situ MeSH
• lidé středního věku MeSH
• lidé MeSH
• orgánové kultury - kultivační techniky MeSH
• senioři MeSH
• thyroxin farmakologie   MeSH
• transformující růstový faktor beta2 metabolismus   MeSH
• trijodthyronin farmakologie   MeSH
• vlasový folikul cytologie   fyziologie   účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• souhrny MeSH