Circadian clock regulation of myofibroblast fate

Abstract

Fibrosis-related disorders represent an increasing medical and economic burden on a worldwide scale, accounting for one-third of all disease-related deaths with limited therapeutic options. As central mediators in fibrosis development, myofibroblasts have been gaining increasing attention in the last 20 years as potential targets for fibrosis attenuation and reversal. While various aspects of myofibroblast physiology have been proposed as treatment targets, many of these approaches have shown limited long-term efficacy so far. However, ongoing research is uncovering new potential strategies for targeting myofibroblast activity, offering hope for more effective treatments in the future. The circadian molecular clock is a feature of almost every cell in the human body that dictates the rhythmic nature of various aspects of human physiology and behavior in response to changes in the surrounding environment. The dysregulation of these rhythms with aging is considered to be one of the underlying reasons behind the development of multiple aging-related chronic disorders, with fibrotic tissue scarring being a common pathological complication among the majority of them. Myofibroblast dysregulation due to skewed circadian clockwork might significantly contribute to fibrotic scar persistence. In the current review, we highlight the role of the circadian clock in the context of myofibroblast activation and deactivation and examine its dysregulation as a driver of fibrogenesis.