Multiple inflammatory and fibrotic signaling pathways

Multiple inflammatory and fibrotic signaling pathways refers to the complex, overlapping networks of molecular signals that drive chronic inflammation and the subsequent development of fibrosis, or tissue scarring. These pathways are initiated by various stimuli, including tissue injury or infection, which trigger the release of pro-inflammatory cytokines like Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-alpha), as well as pro-fibrotic factors such as Transforming Growth Factor-beta (TGF-beta) (Wynn, T. A., 2008, J. Pathol.). These mediators activate downstream intracellular signaling cascades, including the Smad, MAPK, and PI3K/Akt pathways, which promote the recruitment of immune cells and the activation of collagen-producing myofibroblasts (Richeldi, L., et al., 2017, NEJM). In many chronic diseases, such as idiopathic pulmonary fibrosis, systemic sclerosis, and chronic kidney disease, these pathways become dysregulated and self-sustaining, leading to progressive organ damage and loss of function. Therapeutic approaches often involve multi-kinase inhibitors like nintedanib or anti-fibrotic agents like pirfenidone that attempt to modulate several of these signaling nodes simultaneously (Walton, K. L., et al., 2017, Front. Pharmacol.). Because this term describes a broad pathological process involving numerous distinct proteins and receptors, it is considered a therapeutic category or mechanism of action rather than a single, specific molecular target.

Other names

Pro-inflammatory and pro-fibrotic signaling cascadesInflammatory-fibrotic axisChronic inflammatory and fibrotic networks

Inhibition of multiple signaling nodes, including tyrosine kinases, cytokine receptors, and intracellular secondary messengers, to disrupt the recruitment of inflammatory cells and the activation of myofibroblasts.