Fibrosis is a pathological process marked by excessive extracellular matrix deposition, ultimately resulting in irreversible tissue damage. This aberrant process manifests across multiple organs, including the skin, lung, cardiovascular system, liver, kidneys, and eyes. However, the underlying mechanisms driving tissue fibrosis remain incompletely elucidated, and effective therapeutics are still lacking. In recent years, increasing attention has turned toward the contribution of mechanical signals to fibrotic progression. Within this context, the Piezo family of mechanosensitive ion channels, recently identified as key mediators of mechanotransduction, has emerged as a compelling focus of investigation in diverse pathological settings. This review summarizes current evidence on the central role of Piezo1 in orchestrating fibrotic responses across various tissues. Moreover, we examine the application of Piezo1 modulators in experimental models and their potential to modulate fibrosis, thereby informing the development of novel antifibrotic interventions. By integrating mechanobiological insights into the study of fibrosis, this work highlights promising translational avenues for advancing therapeutic strategies and improving clinical outcomes in fibrotic disease.

Renal fibrosis is a complex and multifactorial process that involves inflammation, cell proliferation, collagen, and fibronectin deposition in the kidney, ultimately leading to chronic kidney disease and even end-stage renal disease. The main goal of treatment is to slow down or halt the progression of fibrosis and to improve or preserve kidney function. Despite significant progress made in understanding the underlying mechanisms of renal fibrosis, current therapies have limited renal protection as the disease progresses. Exosomes derived from stem cells are a newer area of research for the treatment of renal fibrosis. Exosomes as nano-sized extracellular vesicles carry proteins, lipids, and nucleic acids, which can be taken up by local or distant cells, serving as mediators of intercellular communication and as drug delivery vehicles. Exosomes deliver molecules that reduce inflammation, renal fibrosis and extracellular matrix protein production, and promote tissue regeneration in animal models of kidney disease. Additionally, they have several advantages over stem cells, such as being non-immunogenic, having low risk of tumor formation, and being easier to produce and store. This review describes the use of natural and engineered exosomes containing therapeutic agents capable of mediating anti-inflammatory and anti-fibrotic processes during both acute kidney injury and chronic kidney disease. Exosome-based therapies will be compared with stem cell-based treatments for tissue regeneration, with a focus on renal protection. Finally, future directions and strategies for improving the therapeutic efficacy of exosomes are discussed.