RUNX1 and TGF‐β signaling cross talk regulates Ca²⁺ ion channels expression and activity during megakaryocyte development

Abstract

transfected cells was associated with down-regulation of TRP ion channel expression. Finally, we demonstrated that TGF-b/SMAD signaling augments the development of MKs derived from CB-CD34 +. Present data suggest that RUNX1/TGF-b pathway cross talk is crucial for MK maturation.

Virodhamine, an endocannabinoid, induces megakaryocyte differentiation by regulating MAPK activity and function of mitochondria

“…We observed that the mean fluorescence intensity of Fluo-3 was increased upon virodhamine treatment as compared to control (n = 3; Figure 4b), the same difference was noticed when we visualized the cells under confocal microscope: distribution of Fluo-3 positive cells was increased upon virodhamine treatment (n = 3; Figure 4c). Buduo et al, 2014;Hirose et al, 2013;Raghuwanshi et al, 2020;Sardina et al, 2010;Tan et al, 2010). Considering the present study results and previous reports, it can be calculated that MAPK signaling and ROS are involved in virodhamine-induced megakaryocytic differentiation.…”

“…Hence, it is possible that cannabinoids may regulate ROS levels by targeting alternative receptors/ion channels such as TRPV1. Earlier studies established that calcium and ROS are necessary for megakaryocytic differentiation and functions (Di Buduo et al, 2014; Hirose et al, 2013; Raghuwanshi et al, 2020; Sardina et al, 2010; Tan et al, 2010). Considering the present study results and previous reports, it can be calculated that MAPK signaling and ROS are involved in virodhamine‐induced megakaryocytic differentiation.…”

“…Fluo‐3 fluorescence was utilized to determine intracellular free Ca2+ levels. The assay was performed as reported elsewhere (Raghuwanshi et al, 2020). The emitted fluorescence intensity of Fluo‐3 was recorded on a fluorescence‐spectrometer at 25°C (excitation 505 nm, emission 526 nm, slit width 5 nm).…”

“…Different other CB receptor agonists (anandamide, phytocannabinoid D-9-tetrahydrocannabinol, and synthetic CB HU 210) have also been reported to decrease mitochondrial membrane potential and increase mitochondrial ROS production (Athanasiou et al, 2007). Interestingly, in a recent report, ROS has been shown to be involved in MK maturation (Raghuwanshi et al, 2020).…”

Comparative hematopoiesis and signal transduction in model organisms

“…TGF‐β induces cell cycle arrest in human hematopoietic cells by an upregulation of the cyclin‐dependent kinase inhibitor, p57KIP2 (Scandura et al, 2004). Recent publications have established that TGF‐β interacts with RUNX1 transcription factor regulating the Ca2+ channels, thereby maintaining the activity of myeloid cell, megakaryocyte, during development in a cell line‐based model (Raghuwanshi et al, 2020). Conditional deletion of TGF‐β‐associated kinase 1 (TAK1) in mice results in hematopoietic failure; however, the connection of TAK1 to TGF‐β signaling is yet to be established (Tang et al, 2008).…”