Substance P promotes diabetic wound healing by modulating inflammation and restoring cellular activity of mesenchymal stem cells

Abstract

Diabetic ulceration is one of the most debilitating complications of diabetes and is the main cause of amputation. The diabetic environment is characterized by prolonged inflammation and abnormal angiogenesis, leading to delayed wound healing. Thus, regulation of inflammation and neovascularization is considered a desirable target for diabetes. The critical purpose of this study was to determine whether systemically administered Substance P (SP) could promote wound healing in diabetic environments via suppression of inflammation, induction of angiogenesis, and mobilization of stem cells. The effect of SP was assessed by analyzing epidermal and dermal recovery, vessel formation, cytokine secretion profile, and the stem cell pool in the circulation and bone marrow. Compared with the vehicle-treated group, the SP-treated group exhibited more rapid wound coverage, reduced infiltration of leukocytes, suppression of injury-mediated enlargement of the spleen and mesenteric lymph nodes, reduced tumor necrosis factor-alpha levels, increased interleukin-10, elevated pool of M2 monocytes and vascular endothelial growth factor levels in the blood. Moreover, the stem cell pool in the bone marrow, which is very low in diabetes, was markedly restored by SP to normal levels, which could provide a favorable environment to facilitate wound healing in diabetes. This result demonstrates, for the first time, a possible application of SP for the treatment of diabetic complications, including diabetic ulcers.

A potential role for the silent information regulator 2 homologue 1 (SIRT1) in periapical periodontitis

“…, Park et al . ). In pulp tissue, SIRT1 plays a role in the immune defence to LPS and heat stress (Lee et al .…”

The analgesic hybrid of dermorphin/substance P and analog of enkephalin improve wound healing in streptozotocin‐induced diabetic rats

“…In our research, we have demonstrated that hybrid peptides AWL3106 and biphalin improve the healing process in the chronic wound in diabetic rats. Previously, numerous studies have shown that topical opioid (endogenous and exogenous) or SP treatment may be potentially beneficial in wound treatment . There were also many studies which mentioned stress that diabetes ulcers inhibited the wound healing process by prolonged inflammatory phase, angiogenesis disorders, and hampered fibroblast proliferation .…”

“…SP enhances the delivery and accumulation of leucocytes, stimulates the production of various cytokines such as IL‐8, IL‐6, IL‐2, vascular endothelial growth factor (VEGF), and the transforming growth factor beta1 (TGF‐β1). It is also involved in angiogenesis, in epidermal cell proliferation as well as capillary and fibroblast proliferation . Another group of neuropeptides involved in these processes are opioid peptides .…”

A review on different methods to increase the efficiency of mesenchymal stem cell‐based wound therapy

“…The main chemotactic activity of EMBP is related to one flavonoid named Cinnamtannin B‐1. Also, the injection of substance‐P, which is a neuropeptide that promotes physiological responses (such as cell migration and proliferation) increases the MSC mobilization into the blood circulation . These MSCs are named MSC SP and are isolated from the peripheral blood circulation, and are extended in vitro.…”