#MIS-C, eine seltene, aber schwere Entzündung nach #COVID19 bei Kindern, wird durch die Reaktivierung des #EpsteinBarr-Virus ausgelöst.
Das #Virus, das meist unbemerkt im Körper bleibt, kann durch eine gestörte #Immunabwehr erneut aktiv werden.
Forschende der #Charité haben entdeckt, dass der Botenstoff #TGFβ diesen Prozess verstärkt. Eine gezielte Hemmung könnte Behandlungswege für MIS-C und möglicherweise auch für #LongCovid eröffnen.
Abstract This paper concerns the effect produced by the components of a conditioned medium (K‑medium), in which mesenchymal human placenta cells (hP-MSC) are cultivated, on the characteristics of Lewis lung carcinoma (LLC) cells in the culture. It is shown for the first time that the K-medium (secretome) components have a prooncogenic effect on LLC cells as evidence by an increase in cell survival rates, LLC cell proliferation stimulation, and a decrease in the level of apoptotic cells. The effect of the K-medium on the adhesion characteristics of LLC cells in the process of their monolayer growth and migration from 3D-cultures is also demonstrated. When the hP-MSC secretome interacts with the cultured LLC cells, the production of proinflammatory cytokines TGF β and Il-6 is observed to grow. At the same time, the proangiogenic factor VEGF remains almost at the same level. Similar changes in the microenvironment during the interaction of mesenchymal and tumor cells may underlie various prooncogenic effects observed in our previous studies with different MSC inoculation methods during the development and metastasis of Lewis lung carcinoma in vivo.
AbstractKDM6A, an X chromosome-linked histone lysine demethylase, was reported to be frequently mutated in many tumor types including breast and bladder cancer. However, the functional role of KDM6A is not fully understood. Using MCF10A as a model of non-tumorigenic epithelial breast cells, we found that silencing KDM6A promoted cell migration and transformation demonstrated by the formation of tumor-like acini in three-dimensional culture. KDM6A loss reduced the sensitivity of MCF10A cells to therapeutic agents commonly used to treat patients with triple-negative breast cancer and also induced TGFβ extracellular secretion leading to suppressed expression of cytotoxic genes in normal human CD8+ T cells in vitro. Interestingly, when cells were treated with TGFβ, de novo synthesis of KDM6A protein was suppressed while TGFB1 transcription was enhanced, indicating a TGFβ/KDM6A-negative regulatory axis. Furthermore, both KDM6A deficiency and TGFβ treatment promoted disorganized acinar structures in three-dimensional culture, as well as transcriptional profiles associated with epithelial-to-mesenchymal transition and metastasis, suggesting KDM6A depletion and TGFβ drive tumor progression.Implications:. Our study provides the preclinical rationale for evaluating KDM6A and TGFβ in breast tumor samples as predictors for response to chemo and immunotherapy, informing personalized therapy based on these findings.
Bi-allelic Emilin 1 LOF causes #Aortopathy
EMILIN1 deficiency👤🐭->
⏬Fibulin 4
⏬LOX
⏫#TGFβ signals
⏬#Elastogenesis
⏬#CollagenFibrillogenesis
Pediatric #AscendingAorticAneurysm
Dr. Gerhard Sengle & Bert Callewaert labs Am J Hum Genet 2022
https://www.cell.com/ajhg/fulltext/S0002-9297(22)00458-X
Tino Eberl
Cytology and Genetics
WikiPathways
Hao Yin