The source of ACE during scar formation is from both bone marrow and skin tissue

Abstract

Angiotensin-converting enzyme (ACE) has been found in the pathogenesis of various fibrosis diseases, and ACE inhibitor (ACEI) may affect wound healing and cutaneous fibrosis. However, there is no scientific evidence as to where the ACE is produced during scar formation. Whether it is from the cutaneous tissue or the bone marrow, or both remains unknown. In this study, we investigated the source of ACE using bone marrow transplantation in genetically modified mice, analyzed the inflammatory milieu and some growth factors in the middle of the wound healing period (4 d after the wound was induced). After having deleted the ACE from bone marrow or skin tissue, the wound/scar width in the low-ACE groups were narrower than those in wild-type (WT) controls. Loosely arranged collagen deposition and reduced vessel density were also detected in ACE-deficient mice. Lower ACE levels during scar formation were also accompanied by lower levels of TGF-β1. In the middle of the wound healing period, ACE levels affected the inflammatory cells significantly. In the mice with a deficiency in ACE, the expression of TGF-β1 and TNF-α decreased, but not that of IL-4. Our findings indicate that both bone marrow and skin tissue release ACE during scar formation. Deleting either of them can affect the inflammatory cells and growth factors and reduce the expression of TGF-β1, resulting in a decreased level of scarring.-Fang, Q.-Q., Wang, X.-F., Zhao, W.-Y., Chen, C.-Y., Zhang, M.-X., Shi, B.-H., Zhang, L.-Y., Tan, W.-Q. The source of ACE during scar formation is from both bone marrow and skin tissue.

Angiotensin‐converting enzyme inhibitor and angiotensin II type 1 receptor blocker: Potential agents to reduce post‐surgical scar formation in humans

“…So, if they can be used topically, the side effects of oral administration can be greatly reduced. To this end, our previous work explored and proved that the ACE participating in scar formation was derived from both bone marrow and local skin tissue, 23 indicating that inhabiting any one of the two ACE sources could probably be beneficial. Thus, we prepared a series of ramipril and losartan creams, and they also achieved significant results in the linear scar model of mice 24 …”

The role of the renin‐angiotensin system in skin physiology and pathophysiology

“…Importantly, the effects of the cutaneous RAS in wound healing are not only determined by changes in receptor expression, but generally, local synthesis of Ang II seems increased after injury as shown by direct measurements of Ang II and by increased expression of ACE. [ 1,2,15,39 ] In this context, the source of ACE seems not only local synthesis, but also “import” by bone marrow‐derived cells. [ 39 ] Moreover, infiltrating mast cells provide chymase, which is another enzyme capable of converting angiotensin I into Ang II.…”

“…[ 1,2,15,39 ] In this context, the source of ACE seems not only local synthesis, but also “import” by bone marrow‐derived cells. [ 39 ] Moreover, infiltrating mast cells provide chymase, which is another enzyme capable of converting angiotensin I into Ang II. [ 40,41 ]…”

“…[ 35,37,48,51 ] The therapeutic efficacy of these pharmacological approaches is supported by two studies showing a reduction in scar formation in mice with global ACE knockout or with tissue‐specific, cutaneous knockout of ACE. [ 37,39 ]…”

Association analysis and expression level of ACE polymorphisms with egg-laying trait in Taihang chicken

“…Mutations in ACE are associated with angiotensinase expression and contribute strongly to the maintenance of homeostasis in the kidney during transcription ( Li et al, 2017 ). ACE is found in the bone marrow and plays an important role in the immune response of cells by influencing key steps in blood cell production, such as hematopoiesis, myelopoiesis, and the development of other cell lines ( Fang et al, 2018 ). Along with the study of the mechanism of action of ACE in different tissues and organs throughout the body, important functions of ACE have been discovered ( Sharma et al, 2020 ).…”