Piezo1-Mediated Mechanotransduction: Orchestrating the Dynamic Response of Podocytes and Parietal Epithelial Cells to Mechanical Stress

Aim: The glomerulus is a specialized microvascular unit that filters plasma through the coordinated function of podocytes and parietal epithelial cells (PECs). From this perspective, the glomerulus functions like a living hydrogeological filtration system. This review aims to integrate mechanobiology and hydrogeology, reframing podocytes and PECs as active regulators in a pressure-driven network, with Piezo1 central to glomerular homeostasis, adaptation, and pathology. Methods: This review integrates existing literature on glomerular biology, mechanosensitive signaling, and epithelial cell function, focusing on podocytes, PECs, and mechanosensitive structures such as the Piezo1 channel. Results: Podocytes form interdigitating foot processes connected by the slit diaphragm, forming both a selective barrier against protein loss and a mechanosensory interface. Through mechanosensitive structures, such as the Piezo1 channel, podocytes detect variations in hydrostatic pressure and transduce these cues into intracellular signaling that regulates permeability and preserves structural integrity. Sustained mechanical stress, however, can compromise podocyte function and viability. PECs line Bowman capsule, forming an impermeable boundary surrounding the filtration core. Once considered passive, PECs exhibit dynamic properties: some retain progenitor-like potential, contributing to repair, whereas others promote fibrosis in disease conditions. In this analogy, blood flow replaces groundwater while the multilayered filtration barrier mirrors stratified geological formations. Podocytes function as biological piezometers—sensing pressure and modulating filtration—while PECs resemble aquicludes, defining impermeable boundaries that can constrain or reshape the system under mechanical or inflammatory challenges. Conclusion: By integrating mechanobiology and hydrogeology, this review reframes the glomerulus as a living, pressure-driven filtration system in which podocytes and PECs act as active regulators rather than passive structural elements, with Piezo1 playing a central role in glomerular homeostasis, adaptation, and pathology.