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dcyphr | Inducible expression of human endoglin during inflammation and wound healing in vivo

Abstract


Vessel formation (angiogenesis) and inflammation are closely related. A protein on the vessel cells called Endoglin (CD105) is involved in angiogenesis. So this study aims to see if CD105 is also involved in inflammation. They used antibody staining to look at CD105 levels during inflammation and angiogenesis. CD105 was found in low levels in most of the tissue throughout the body. But, it was found at high levels in capillaries near hair follicles, alveoli, and lymph nodes. During wound healing, inflammation and angiogenesis both occur. CD105 levels increase during wound healing. CD105 also moves white blood cells across the vessel membrane and into the target tissue, called leukocyte extravasation. This process happens during wound healing because the body is trying to fight off any infection from entering the broken skin.


Introduction


Many inflammatory diseases also have high levels of angiogenesis. CD105 is responsible for helping form new vessels. Then, it helps smooth muscle form around some of the larger vessels like arterioles. CD105 works with transforming growth factor beta 1 (TGF beta-1) and 2 (TGF beta-2) to help the smooth muscle form around the vessel. Mutations causing low levels of CD105 are usually fatal before birth in mammals. High levels of CD105 can lead to atherosclerosis, nephritis, psoriasis, and tumors.


Materials and Methods


Skin, lung, and liver tissue were studied because these commonly have disease in the vessels. The volunteers in this study each had a small biopsy taken from their buttock region. They were monitored for the next 28 days.

Antibody staining (immunohistochemisty) was used to look at wound healing. They looked for CD105, macrophages, T cells, and proliferation markers. Proliferation markers tell us if the cells are rapidly growing.


Results


Inflamed Tissue - CD105 in Inflammation

This study did not detect CD105 in most normal, healthy tissue. The only normal tissue with high levels of CD105 were in capillaries around hair follicles, alveoli, and lymph nodes. The expression of CD105 is very high in inflamed tissue. A lot of inflammation is caused by white blood cells rushing to the target tissue, and CD105 is the protein that allows the white blood cells to cross the membrane.


Wound Healing - Cd105 in Angiogenesis

The researchers took biopsies of wounds in the process of healing at 0, 1, 4, 7, 14, and 28 days after the wound. CD105 increased by 3 to 8 times between day 0 and day 7. The increase began at day 1 or 2 and stayed at a high level until they began dropping on day 28. Activated and proliferating vessel cells were both present in the biopsy and assessed for CD105 levels. Activated cells are cells that were present during the wound. Proliferating cells are cells that have grown after the wound first occurred. High levels of CD105 were found in both activated and proliferating vessel cells. CD105 was not found in white blood cells or smooth muscle. But, higher levels of CD105 were found in a cell called a myofibroblast. Myofibroblasts help to repair muscle in wounds. The CD105 RNA was increased similar to the protein levels.


Discussion


This study showed that CD105 levels are high in both inflammation and angiogenesis conditions. CD105 levels are high during extravasation, where many white blood cells need to cross the vessel walls into the tissue. This suggests that CD105 facilitates this process.

Myofibroblasts were found to have high levels of CD105 in wounds. Myofibroblasts interact with TGF-beta1, which is known to work with CD105. In wound healing, CD105 is at a maximum level when angiogenesis and white blood cell extravasation are both happening. CD105 protein and RNA levels are both increased during wound healing. This tells us that CD105 is not a byproduct of wound healing and the body wants more of it to help the wound heal faster.

TGF-beta1 normally slows the growth of vessels. CD105 increases the growth of vessels. High levels of TGF-beta1 cause CD105 levels to increase too. This shows us that these two work together to balance the growth of vessels. If TGF-beta1 levels get too high, CD105 will increase and counter TGF-beta1’s effects on blood vessel growth.

CD105 may be a great target in the treatment of chronic wounds, inflammatory diseases, and tumors.