Piezo initiates transient production of collagen IV to repair damaged basement membranes

Abstract

SummaryBasement membranes are sheets of extracellular matrix separating tissue layers and providing mechanical support. Their mechanical properties are determined largely by their most abundant protein, Collagen IV (Col4). Although basement membranes are repaired after damage, little is known about how. To wit, since basement membrane is extracellular it is unknown how damage is detected, and since Col4 is long-lived it is unknown how it is regulated to avoid fibrosis. Using the basement membrane of the adultDrosophilamidgut as a model, we show that repair is distinct from maintenance. In healthy conditions, midgut Col4 originates from the fat body, but after damage, a subpopulation of enteroblasts we term “matrix menders” transiently express Col4, and Col4 from these cells is required for repair. Activation of the mechanosensitive channel Piezo is required for matrix menders to upregulate Col4, and the signal to initiate repair is a reduction in basement membrane stiffness. Our data suggests that mechanical sensitivity may be a general property of Col4-producing cells.Graphical abstract