麻豆淫院

A new study by Vanderbilt investigators has uncovered a previously unknown biological mechanism: how tissues detect and respond to damage in basement membranes, the thin layers of extracellular matrix that surround and support nearly every organ in the body.

The research, in Developmental Cell, is the first to show how local cells sense and respond to changes in basement membrane stiffness caused by damage鈥攁nd how they activate a previously unknown set of "matrix mender" cells to repair the tissue. The results of this study have far-reaching implications, as basement membrane damage plays a role in numerous diseases, including diabetes, dementia, and cancer.

Basement membranes are extracellular matrices鈥攆lat sheets of protein and carbohydrate鈥攖hat are essential for tissue architecture and function. But like all tissues, they are subject to damage. Until now, how the body notices and heals damage to these basement membranes has remained a mystery.

"Virtually nothing was known about how the damaged matrix is detected and repaired," researcher Andrea Page-McCaw said. "Basement membranes lie outside cells, and we wanted to know how cells know when the membranes are damaged and how they get repaired."

Page-McCaw, Stevenson Professor and professor of cell and developmental biology, led the research along with a recent graduate student from her lab, Aubrie Stricker.

Studying basement membranes is challenging, however, because they are best studied in an intact animal. If you remove them from the animal, Page-McCaw said, you change their organization and their relationship to other cells and fluids. For this study, the team worked entirely on living organisms and performed precise genetic manipulations in fruit flies, preserving the natural environment of basement membranes and allowing the team to study how they function in real time.

Page-McCaw and Stricker employed advanced in vivo imaging techniques to observe basement membrane dynamics within the fruit flies' intact digestive systems. To sort through the complex imaging data they collected, the researchers used automated image analysis methods, which enabled precise quantification of the changes in tissue stiffness.

"Vandy has a highly collaborative atmosphere, and we were able to get help with automated image analysis from our colleague Shane Hutson," said Page-McCaw. Hutson is a professor of physics.

The authors uncovered three key results:

• Local cells monitor basement membrane integrity by sensing mechanical stiffness鈥攅ssentially using touch to detect injury.
• Piezo channels, special proteins in cells that can sense physical pressure or stretch, detect the stiffness. When they feel mechanical force, they send signals that help cells respond.
• When Piezo channels detect damage, their activity triggers the generation of new cells鈥攄ubbed "matrix menders"鈥攚hose job is to fix the local basement membrane.

"It was a very exciting day when Aubrie discovered that Piezo is required for the matrix menders to appear," Page-McCaw said.

Although the research was conducted on fruit flies, the implications extend to human health. Understanding how the body detects and repairs such damage may lead to new therapeutic approaches in regenerative and sports medicine, and in various diseases such as diabetes, dementia, and cancer.

Although the researchers have determined the role of the Piezo channels in sensing damage, the team hopes to determine which cell type uses them to sense stiffness. They hypothesize that stem cells鈥攐ften found in close contact with basement membranes鈥攎ight be cells involved in repair. If so, it could reshape our understanding of how stem cells maintain tissue integrity across the body.