麻豆淫院

One of the most significant moments in the evolutionary journey of life on this planet was the transition from water to land. This huge step required animals to adapt to new challenges, including supporting their body weight and developing new modes of locomotion. These changes put increased pressure on weight-bearing skin, such as paws and soles.

Despite its importance, the molecular mechanisms by which skin maintains its stability (homeostasis) under this constant pressure have been poorly understood. However, in a paper in the journal Cell, scientists from China have revealed new insights into how skin adapts to these physical forces.

To better understand what happens, the researchers focused on the Slurp1 gene, which provides instructions for making a protein (SLURP1) found in skin cells and other cells that line the surfaces and cavities of the body. It is present in amphibians, reptiles, birds and mammals but not in invertebrates and fish. This suggests that it could've emerged alongside terrestrial adaptation.

Researchers created "knockout" mice, meaning they were designed to be missing the Slurp1 gene. They also created mice that couldn't produce the SLURP1 protein. These were compared with a control group of regular mice.

Next, they experimented with how the mice's paws responded to different types of physical pressure. The team also zeroed in on what was happening at the cellular level, looking at which genes were turned on and off and which proteins were being produced.

Key findings

The study found that the SLURP1 protein is present in weight-bearing regions such as the paws, suggesting its importance in managing physical pressure. In mice that were missing this protein, normal pressure on their paws caused their skin to become abnormally thick and develop a condition similar to a human disease called PPK (palmoplantar keratoderma). When they took the pressure off the paws, the skin returned to normal, meaning the symptoms were a direct result of this stress.

The paper also revealed that the protein has a more important job in the cell than previously thought. It acts as an endoplasmic reticulum (ER) membrane protein and protects a critical pump inside the ER when it is under mechanical stress. This helps the cell maintain its stability.

"Our findings reveal a previously unrecognized ER-based mechano-resistance mechanism essential for maintaining epidermal homeostasis and regulating regenerative responses under mechanical load," wrote Dr. Ting Chen, the paper's senior author.

This research not only gives us valuable insights into the evolutionary past that made terrestrial life possible, but it also has implications for modern medicine. The findings could lead to new, targeted treatments for PPK and other skin diseases. Additionally, this new understanding of how skin adapts to pressure could help with the design of biomaterials or prosthetics that fit and work better with human skin.

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