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Sphingosine 1-phosphate accelerates wound healing in diabetic mice.
J Dermatol Sci 2007; 48(1):53-60JD

Abstract

BACKGROUND

Blood platelets store sphingosine 1-phosphate (S1P) abundantly and release this bioactive lipid extracellularly. S1P acts as an intercellular mediator through interaction with the endothelial differentiation gene (EDG)/S1P family of G protein-coupled receptors. Of the EDG family S1P receptors, EDG-5 (S1P2) is inhibited in migration induced by S1P. Diabetes impairs numerous aspects of tissue repair. Failure of wound angiogenesis is known to delay diabetic wound healing.

OBJECTIVES

We examined whether S1P subcutaneous injection could improve the healing of full-thickness skin wounds in healthy and diabetic mice. We further determine if the combined S1P and EDG-5 (S1P2) antagonist injection in diabetic mice could affect wound healing. Finally, we examined the histopathological findings of the wound following S1P injection in diabetic mice.

METHODS

Eight- to 10-week-old BALA/c mice, diabetic db/db mice and Wister rats were used for the studies. A full-thickness wound was made on the dorsal skin of the healthy and diabetic mice. Either 10 microM or 100 microM of S1P or vehicle control (BSA/PBS) was injected into the wound bed every day. We calculated the wound area after each injection. EDG-5 (S1P2) antagonist (JTE-013) or vehicle (DMSO) was then injected in addition to the S1P around the dorsal wound of diabetic mice and the wound diameter was measured. Wound tissue samples were excised following injection for histopathological examination.

RESULTS

Wound area in normal BALA/c mice did not significantly decrease upon S1P injection compared to S1P-untreated controls. S1P injection alone showed significant promotion of wound healing in diabetic mice compared to no S1P treatment. The combination of S1P and EDG-5 (S1P2) receptor antagonist administration induced maximal wound healing in diabetic mice. Histopathological examination revealed that S1P induces neo-vascularization potential in rats and diabetic mice wound.

CONCLUSIONS

S1P injection in diabetic mice significantly accelerated cutaneous wound healing in the neo-vascularization process. The results demonstrate that S1P affects and sustains all key cellular processes responsible for wound repair and point to a unique potential for this molecule in the therapy of diabetic wounds, particularly as an angiogenic agent in treatment of diabetic wounds.

Authors+Show Affiliations

Department of Dermatology, St. Marianna University School of Medicine, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17643267

Citation

Kawanabe, Takeshi, et al. "Sphingosine 1-phosphate Accelerates Wound Healing in Diabetic Mice." Journal of Dermatological Science, vol. 48, no. 1, 2007, pp. 53-60.
Kawanabe T, Kawakami T, Yatomi Y, et al. Sphingosine 1-phosphate accelerates wound healing in diabetic mice. J Dermatol Sci. 2007;48(1):53-60.
Kawanabe, T., Kawakami, T., Yatomi, Y., Shimada, S., & Soma, Y. (2007). Sphingosine 1-phosphate accelerates wound healing in diabetic mice. Journal of Dermatological Science, 48(1), pp. 53-60.
Kawanabe T, et al. Sphingosine 1-phosphate Accelerates Wound Healing in Diabetic Mice. J Dermatol Sci. 2007;48(1):53-60. PubMed PMID: 17643267.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sphingosine 1-phosphate accelerates wound healing in diabetic mice. AU - Kawanabe,Takeshi, AU - Kawakami,Tamihiro, AU - Yatomi,Yutaka, AU - Shimada,Shinji, AU - Soma,Yoshinao, Y1 - 2007/07/20/ PY - 2007/03/13/received PY - 2007/06/12/revised PY - 2007/06/12/accepted PY - 2007/7/24/pubmed PY - 2007/12/28/medline PY - 2007/7/24/entrez SP - 53 EP - 60 JF - Journal of dermatological science JO - J. Dermatol. Sci. VL - 48 IS - 1 N2 - BACKGROUND: Blood platelets store sphingosine 1-phosphate (S1P) abundantly and release this bioactive lipid extracellularly. S1P acts as an intercellular mediator through interaction with the endothelial differentiation gene (EDG)/S1P family of G protein-coupled receptors. Of the EDG family S1P receptors, EDG-5 (S1P2) is inhibited in migration induced by S1P. Diabetes impairs numerous aspects of tissue repair. Failure of wound angiogenesis is known to delay diabetic wound healing. OBJECTIVES: We examined whether S1P subcutaneous injection could improve the healing of full-thickness skin wounds in healthy and diabetic mice. We further determine if the combined S1P and EDG-5 (S1P2) antagonist injection in diabetic mice could affect wound healing. Finally, we examined the histopathological findings of the wound following S1P injection in diabetic mice. METHODS: Eight- to 10-week-old BALA/c mice, diabetic db/db mice and Wister rats were used for the studies. A full-thickness wound was made on the dorsal skin of the healthy and diabetic mice. Either 10 microM or 100 microM of S1P or vehicle control (BSA/PBS) was injected into the wound bed every day. We calculated the wound area after each injection. EDG-5 (S1P2) antagonist (JTE-013) or vehicle (DMSO) was then injected in addition to the S1P around the dorsal wound of diabetic mice and the wound diameter was measured. Wound tissue samples were excised following injection for histopathological examination. RESULTS: Wound area in normal BALA/c mice did not significantly decrease upon S1P injection compared to S1P-untreated controls. S1P injection alone showed significant promotion of wound healing in diabetic mice compared to no S1P treatment. The combination of S1P and EDG-5 (S1P2) receptor antagonist administration induced maximal wound healing in diabetic mice. Histopathological examination revealed that S1P induces neo-vascularization potential in rats and diabetic mice wound. CONCLUSIONS: S1P injection in diabetic mice significantly accelerated cutaneous wound healing in the neo-vascularization process. The results demonstrate that S1P affects and sustains all key cellular processes responsible for wound repair and point to a unique potential for this molecule in the therapy of diabetic wounds, particularly as an angiogenic agent in treatment of diabetic wounds. SN - 0923-1811 UR - https://www.unboundmedicine.com/medline/citation/17643267/Sphingosine_1_phosphate_accelerates_wound_healing_in_diabetic_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0923-1811(07)00217-4 DB - PRIME DP - Unbound Medicine ER -