Noncoding RNAs: Master Regulator of Fibroblast to Myofibroblast Transition in Fibrosis

Abstract

Myofibroblasts escape apoptosis and proliferate abnormally under pathological conditions, especially fibrosis; they synthesize and secrete a large amount of extracellular matrix (ECM), such as α-SMA and collagen, which leads to the distortion of organ parenchyma structure, an imbalance in collagen deposition and degradation, and the replacement of parenchymal cells by fibrous connective tissues. Fibroblast to myofibroblast transition (FMT) is considered to be the main source of myofibroblasts. Therefore, it is crucial to explore the influencing factors regulating the process of FMT for the prevention, treatment, and diagnosis of FMT-related diseases. In recent years, non-coding RNAs, including microRNA, long non-coding RNAs, and circular RNAs, have attracted extensive attention from scientists due to their powerful regulatory functions, and they have been found to play a vital role in regulating FMT. In this review, we summarized ncRNAs which regulate FMT during fibrosis and found that they mainly regulated signaling pathways, including TGF-β/Smad, MAPK/P38/ERK/JNK, PI3K/AKT, and WNT/β-catenin. Furthermore, the expression of downstream transcription factors can be promoted or inhibited, indicating that ncRNAs have the potential to be a new therapeutic target for FMT-related diseases.

Newly discovered functions of miRNAs in neuropathic pain: Transitioning from recent discoveries to innovative underlying mechanisms

“… 76 On the other hand, MAPK, a mitogen-activated kinase, plays a significant role in various physiological and pathological processes, including neuropathic pain, through the phosphorylation of serine/threonine and tyrosine residues. 77 At the same time, a distinct set of proteins called cytokine signaling inhibitors (SOCS) maintains the equilibrium of Th2-Th1 cells, moderates the negative feedback of cytokine signaling, and lessens Th2-induced inflammation. SOCS1 and SOCS3 activation by various inflammatory and anti-inflammatory cytokines inhibits cytokine actions.…”

Emerging roles of miRNAs in neuropathic pain: From new findings to novel mechanisms

“…The M1 and M2 macrophages are activated by the activation of the NF-κB pathway, which causes them to release pro-inflammatory cytokines and speed up the inflammatory response process (Poladian et al, 2023). Meanwhile, MAPK is a mitogen activated kinase that controls a number of physiological and pathological processes, including NP, by phosphorylating serine/threonine and tyrosine (Zhang et al, 2023). However, the balance of Th1-Th2 cells, the control of cytokine signaling negative feedback, and the reduction of Th2-induced inflammation are all regulated by a unique family of proteins known as cytokine signaling inhibitors (SOCS).…”

AMPK signaling inhibits the differentiation of myofibroblasts: impact on age-related tissue fibrosis and degeneration

“…While there is convincing evidence that the differentiation and transdifferentiation processes of myofibroblasts are under epigenetic regulation, such as DNA methylation and noncoding RNAs (Hu et al 2010 ; Mann et al 2010 ; Zhang et al 2023 ), the fundamental epigenetic mechanisms are currently poorly understood. However, it is known that there is a wide variety of mechanical and physical inducers and signaling pathways capable of triggering the differentiation of myofibroblasts (D’Urso and Kurniawan 2020 ; Pakshir et al 2020 ).…”