Substance P ameliorates tumor necrosis factor‐alpha‐induced endothelial cell dysfunction by regulating <scp>eNOS</scp> expression in vitro

Piao, Jiyuan; Hong, Hoon Pyo; Son, Youngsook

doi:10.1111/micc.12443

Cited by 16 publications

(16 citation statements)

References 32 publications

(61 reference statements)

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“…After 24 h, SP was added to the damaged ADSCs at a concentration of 100 nM ( Figure 2 A). This dose of SP was determined based on previous reports [ 15 , 16 , 17 ].…”

Section: Resultsmentioning

confidence: 99%

“…Substance-P (SP) is an endogenous neuropeptide that interacts with neurokinin receptor 1 (NK-1R). SP has been reported to stimulate cell proliferation and prevent apoptosis under inflammatory or oxidative stress by activating the extracellular signal-regulated kinases 1/2 (ERK 1/2) or Akt and by translocating β-catenin to cell nuclei [ 15 , 16 , 17 , 18 ]. SP could suppress inflammation to promote tissue repair in severe diseases by modulating the immune cell profile in circulation-associated and lymphoid organs [ 19 , 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Substance-P Restores Cellular Activity of ADSC Impaired by Oxidative Stress

et al. 2020

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Oxidative stress induces cellular damage, which accelerates aging and promotes the development of serious illnesses. Adipose-derived stem cells (ADSCs) are novel cellular therapeutic tools and have been applied for tissue regeneration. However, ADSCs from aged and diseased individuals may be affected in vivo by the accumulation of free radicals, which can impair their therapeutic efficacy. Substance-P (SP) is a neuropeptide that is known to rescue stem cells from senescence and inflammatory attack, and this study explored the restorative effect of SP on ADSCs under oxidative stress. ADSCs were transiently exposed to H2O2, and then treated with SP. H2O2 treatment decreased ADSC cell viability, proliferation, and cytokine production and this activity was not recovered even after the removal of H2O2. However, the addition of SP increased cell viability and restored paracrine potential, leading to the accelerated repopulation of ADSCs injured by H2O2. Furthermore, SP was capable of activating Akt/GSK-3β signaling, which was found to be downregulated following H2O2 treatment. This might contribute to the restorative effect of SP on injured ADSCs. Collectively, SP can protect ADSCs from oxidant-induced cell damage, possibly by activating Akt/GSK-3β signaling in ADSCs. This study supports the possibility that SP can recover cell activity from oxidative stress-induced dysfunction.

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“…After 24 h, SP was added to the damaged ADSCs at a concentration of 100 nM ( Figure 2 A). This dose of SP was determined based on previous reports [ 15 , 16 , 17 ].…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Substance-P Restores Cellular Activity of ADSC Impaired by Oxidative Stress

et al. 2020

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“…SP is known to suppress highly activated immune response [ 35 – 37 , 43 ], protect the vascular endothelium [ 42 ], and restore stem cell functions [ 40 , 41 ] under disease conditions. These functions were proven in different non-clinical disease models.…”

Section: Discussionmentioning

confidence: 99%

“…SP, a new BMSC mobilizer [ 38 ], can not only restore the BMSC pool by repopulating BMSCs [ 39 ] but also block their senescence by potentiating their ability to secrete anti-inflammatory cytokines [ 40 , 41 ]. Moreover, SP protects the vascular endothelium and promotes angiogenesis to inhibit the progression of vascular diseases [ 42 – 44 ]. Interestingly, the expression of SP in BM is severely decreased and that of its receptor NK-1R is enhanced in osteoporosis [ 45 , 46 ], indicative of its relevance to bone formation.…”

Section: Introductionmentioning

confidence: 99%

Substance P blocks ovariectomy-induced bone loss by modulating inflammation and potentiating stem cell function

Piao¹,

Park²,

Hwang³

et al. 2020

aging

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Osteoporosis is an age-related disease caused by imbalanced bone remodeling resulting from excessive bone resorption. Osteoporosis is tightly linked with induction of chronic inflammation, which activates osteoclasts and impairs osteoprogenitor in bone marrow. T helper 17 (Th17) cells have been recently recognized as one of major inducers in the pathophysiology of bone loss by secreting IL-17. Thus, modulation of Th17 development is anticipated to affect the progression of osteoporosis. Substance P (SP) is reported to provide anti-inflammatory effects by controlling immune cell profile and also, promote restoration of damaged stem cell niches—the bone marrow—by repopulating BMSCs or potentiating its paracrine ability. This study aimed to explore the therapeutic effects of systemically injected SP on ovariectomy (OVX)-induced osteoporosis. Resultantly, SP injection obviously blocked OVX-induced impairment of bone microarchitecture and reduction of the mineral density. In osteoporotic condition, SP could ameliorate chronic inflammation by promoting Treg cell polarization and inhibiting the development of osteoclastogenic Th17 cells. Moreover, SP could rejuvenate stem cell and enable stem cells to repopulate and differentiate into osteoblast. Collectively, our study strongly suggests that SP treatment can block osteoporosis and furthermore, SP treatment provides therapeutic effect on chronic disease with inflammation and stem cell dysfunction.

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“…Hong et al demonstrated that SP acts not only as a messenger that indicates injury but also as a mobilizer of CD29 + stromal-like cells, which are produced in the bone marrow and participate in wound healing (14). Recent studies have shown that SP has an anti-inflammatory effect by inhibiting tumor necrosis factor-alpha (TNF-α) and inducing IL-10 (15)(16)(17). In the case of ischemia reperfusion injury (IRI), SP improves the injury by increasing MSC and endothelial progenitor cell (EPC) in the blood circulation and reducing TNFα (18).…”

Section: Introductionmentioning

confidence: 99%

Substance P Improves Renal Ischemia Reperfusion Injury Through Modulating Immune Response

et al. 2020

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Substance P (SP), an injury-inducible messenger that mobilizes bone marrow stem cells and modulates the immune response, has been suggested as a novel target for therapeutic agents. We evaluated the role of SP as an immune cell modulator during the progression of renal ischemic/reperfusion injury (IRI). Unilateral IRI induced the transient expression of endogenous SP and the infiltration of CCR7 + M1 macrophages in injured kidneys. However, SP altered the intrarenal macrophage polarization from CCR7 + M1 macrophages to CD206 + M2 macrophages in injured kidneys. SP also modulated bone marrow-derived neutrophils and mesenchymal stromal cells after IRI. SP treatment for 4 weeks starting one week after unilateral IRI significantly preserved kidney size and length and normal tubular structures and alleviated necrotic tubules, inflammation, apoptosis, and tubulointerstitial fibrosis. The beneficial effects of SP were accompanied by attenuation of intrarenal recruitment of CD4, CD8, and CD20 cells and abnormal angiogenesis. The immunomodulatory effect of SP suggested that SP could be a promising therapeutic target for preventing the progression of acute kidney injury to chronic kidney disease.

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Substance P ameliorates tumor necrosis factor‐alpha‐induced endothelial cell dysfunction by regulating eNOS expression in vitro

Abstract: SP can protect the vascular endothelium against inflammation-induced damage through modulation of the Akt/eNOS/NO signaling pathway.

Cited by 16 publications

References 32 publications

Substance-P Restores Cellular Activity of ADSC Impaired by Oxidative Stress

Substance-P Restores Cellular Activity of ADSC Impaired by Oxidative Stress

Substance P blocks ovariectomy-induced bone loss by modulating inflammation and potentiating stem cell function

Substance P Improves Renal Ischemia Reperfusion Injury Through Modulating Immune Response

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