Therapeutic Strategies for Organ Fibrosis: Decoding Molecular Mechanisms and Pro-repair Pathways

Organ fibrosis represents a major challenge in molecular medicine, contributing to over one-third of global mortality. It is a pathological consequence of unresolved injury and maladaptive tissue repair, characterized by persistent fibroblast activation, excessive extracellular matrix deposition, and irreversible loss of organ function. Idiopathic pulmonary fibrosis, liver fibrosis associated with metabolic dysfunction, and chronic kidney fibrosis exemplify diseases where the fibrotic process becomes self-perpetuating. Despite decades of investigation, current antifibrotic treatments only slow progression rather than achieve reversal. Recent advances in molecular biosciences have revealed key regulatory nodes—such as signaling crosstalk among fibroblasts, immune cells, epithelial/endothelial compartments, and extracellular matrix components—that govern the switch between regenerative healing and chronic fibrosis. However, a detailed molecular understanding of how injury cues transition toward pro-repair remodeling remains incomplete, highlighting the need to decipher the regulatory circuits that determine fibrotic versus regenerative outcomes.This Research Topic aims to elucidate the molecular mechanisms underlying fibrotic transformation and to identify therapeutic strategies capable of restoring tissue integrity. Specifically, it seeks to bridge the knowledge gap between pathological scarring and functional repair by focusing on the modulation of cellular and molecular pathways that govern tissue regeneration. We welcome contributions that explore how intrinsic repair programs are suppressed during chronic damage, how cell death modalities influence fibrotic remodeling, and how developmental or regenerative cues can be re-engaged therapeutically. Mechanistic insights into the role of fibroblast plasticity, immune–stromal communication, and pro-repair epigenetic reprogramming are particularly encouraged, as these understanding may lead to novel interventions capable of halting or reversing fibrosis across organ systems.To gather further insights into the mechanisms orchestrating the transition from fibrosis to repair, we welcome articles addressing, but not limited to, the following themes:o Molecular and cellular mechanisms of tissue regeneration: dissection of intrinsic signaling pathways that promote repair in lung, liver, kidney, heart, and other organs.o Regulated cell death and fibrotic progression: how apoptosis, ferroptosis, necroptosis, or pyroptosis modulate the repair–fibrosis balance.o Therapeutic activation of pro-repair pathways: novel molecular targets, small molecules, biologics, or gene-based therapies for antifibrotic intervention.o Epigenetic and transcriptional regulation of fibrosis resolution: reprogramming cell fate to favor regenerative over fibrotic trajectories.o Innovative translational models: organoids, multi-omics, and in vivo models that capture the switch dynamics from injury to repair.Article types welcomed include Original Research, Review, Mini Review, Hypothesis and Theory, and Perspective papers. Topic editors: Chunheng Mo, Przemysław J Kotyla, Sandeep Kumar Source: https://www.frontiersin.org/research-topics/82615/therapeutic-strategies-for-organ-fibrosis-decoding-molecular-mechanisms-and-pro-repair-pathways