Search results for "mitogen-activated protein kinase 14"
showing 5 items of 5 documents
Liver-specific p38α deficiency causes reduced cell growth and cytokinesis failure during chronic biliary cirrhosis in mice
2012
p38α mitogen-activated protein kinases (MAPK) may be essential in the up-regulation of proinflammatory cytokines and can be activated by transforming growth factor β, tumor necrosis factor-α, interleukin-1β, and oxidative stress. p38 MAPK activation results in hepatocyte growth arrest, whereas increased proliferation has been considered a hallmark of p38α-deficient cells. Our aim was to assess the role of p38α in the progression of biliary cirrhosis induced by chronic cholestasis as an experimental model of chronic inflammation associated with hepatocyte proliferation, apoptosis, oxidative stress, and fibrogenesis. Cholestasis was induced in wildtype and liver-specific p38α knockout mice by…
Pharmacological targeting of the novel β-catenin chromatin-associated kinase p38α in colorectal cancer stem cell tumorspheres and organoids
2021
AbstractThe prognosis of locally advanced colorectal cancer (CRC) is currently unsatisfactory. This is mainly due to drug resistance, recurrence, and subsequent metastatic dissemination, which are sustained by the cancer stem cell (CSC) population. The main driver of the CSC gene expression program is Wnt signaling, and previous reports indicate that Wnt3a can activate p38 MAPK. Besides, p38 was shown to feed into the canonical Wnt/β-catenin pathway. Here we show that patient-derived locally advanced CRC stem cells (CRC-SCs) are characterized by increased expression of p38α and are “addicted” to its kinase activity. Of note, we found that stage III CRC patients with high p38α levels display…
p38α regulates actin cytoskeleton and cytokinesis in hepatocytes during development and aging.
2017
[Background]: Hepatocyte poliploidization is an age-dependent process, being cytokinesis failure the main mechanism of polyploid hepatocyte formation. Our aim was to study the role of p38α MAPK in the regulation of actin cytoskeleton and cytokinesis in hepatocytes during development and aging. [Methods]: Wild type and p38α liver-specific knock out mice at different ages (after weaning, adults and old) were used. [Results]: We show that p38α MAPK deficiency induces actin disassembly upon aging and also cytokinesis failure leading to enhanced binucleation. Although the steady state levels of cyclin D1 in wild type and p38α knock out old livers remained unaffected, cyclin B1- a marker for G2/M…
p38α MAPK is required for contact inhibition
2005
Proliferation of nontransformed cells is regulated by cell-cell contacts, which are referred to as contact-inhibition. Despite its generally accepted importance for cell cycle control, knowledge about the intracellular signalling pathways involved in contact inhibition is scarce. In the present work we show that p38alpha mitogen-activated protein kinase (MAPK) is involved in the growth-inhibitory signalling cascade of contact inhibition in fibroblasts. p38alpha activity is increased in confluent cultures of human fibroblasts compared to proliferating cultures. Time course studies show a sustained activation of p38alpha in response to cell-cell contacts in contrast to a transient activation …
Selective p38α MAP kinase/MAPK14 inhibition in enzymatically modified LDL-stimulated human monocytes: implications for atherosclerosis.
2016
The first ATP-competitive p38α MAPK/MAPK14 inhibitor with excellent in vivo efficacy and selectivity, skepinone-L, is now available. We investigated the impact of selective p38α MAPK/MAPK14 inhibition on enzymatically modified LDL (eLDL) stimulated human monocytes with its implications for atherosclerosis. Among the different p38 MAPK isoforms, p38α/MAPK14 was the predominantly expressed and activated isoform in isolated human peripheral blood monocytes. Moreover, eLDL colocalized with macrophages positive for p38α MAPK/MAPK14 in human carotid endarterectomy specimens. Using the human leukemia cell line THP-1 and/or primary monocyte-derived macrophages, skepinone-L inhibited eLDL-induced ac…