upregulation

Upregulation is a cellular process in which a cell increases the amount, density, or responsiveness of a particular molecular component, most commonly receptors, but also including enzymes or transporters. It typically occurs in response to reduced stimulation, chronic blockade of signaling, or increased demand for a signaling pathway, and it can enhance a cell’s sensitivity to a signal.

Mechanisms underlying upregulation include transcriptional activation that increases mRNA production, followed by higher protein synthesis. Other routes involve stabilization of mRNA or protein, reduced degradation, and trafficking of intracellular stores to the plasma membrane or to functional sites. Epigenetic changes can also raise the baseline level of transcription for a given gene. In receptor upregulation, signaling may recruit intracellular receptor pools to the cell surface, augmenting receptor density and responsiveness.

Contexts and examples include receptor upregulation in response to low ligand availability or to pharmacological antagonists, which can heighten sensitivity to the ligand when it becomes available again. Upregulation can also occur for enzymes, transporters, or other signaling molecules as part of adaptive responses. In immunology, activation can increase surface expression of certain adhesion or costimulatory molecules, altering cell interactions.

Relation to downregulation is important: upregulation is the opposite of downregulation, where signaling reduces receptor numbers or activity. Clinically, upregulation can influence drug effects, tolerance, and disease progression. Measurement methods include assessing mRNA levels (e.g., qPCR), total protein (Western blot, ELISA), and cell-surface receptors (flow cytometry, radioligand binding).