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Wound healing is accelerated by agonists of adenosine A2 (G alpha s-linked) receptors.

Montesinos MC, Gadangi P, Longaker M, Sung J, Levine J, Nilsen D, Reibman J, Li M, Jiang CK, Hirschhorn R, Recht PA, Ostad E, Levin RI, Cronstein BN - J. Exp. Med. (1997)

Bottom Line: In rats rendered diabetic (streptozotocin-induced diabetes mellitus) wound healing was impaired as compared to nondiabetic rats; CGS-21680 significantly increased the rate of wound healing in both nondiabetic and diabetic rats.Indeed, the rate of wound healing in the CGS-21680-treated diabetic rats was greater than or equal to that observed in untreated normal rats.These results appear to constitute the first evidence that a small molecule, such as an adenosine receptor agonist, accelerates wound healing in both normal animals and in animals with impaired wound healing.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, New York University Medical Center, New York 10016, USA.

ABSTRACT
The complete healing of wounds is the final step in a highly regulated response to injury. Although many of the molecular mediators and cellular events of healing are known, their manipulation for the enhancement and acceleration of wound closure has not proven practical as yet. We and others have established that adenosine is a potent regulator of the inflammatory response, which is a component of wound healing. We now report that ligation of the G alpha s-linked adenosine receptors on the cells of an artificial wound dramatically alters the kinetics of wound closure. Excisional wound closure in normal, healthy mice was significantly accelerated by topical application of the specific A2A receptor agonist CGS-21680 (50% closure by day 2 in A2 receptor antagonists. In rats rendered diabetic (streptozotocin-induced diabetes mellitus) wound healing was impaired as compared to nondiabetic rats; CGS-21680 significantly increased the rate of wound healing in both nondiabetic and diabetic rats. Indeed, the rate of wound healing in the CGS-21680-treated diabetic rats was greater than or equal to that observed in untreated normal rats. These results appear to constitute the first evidence that a small molecule, such as an adenosine receptor agonist, accelerates wound healing in both normal animals and in animals with impaired wound healing.

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Endothelial cells  (HUVEC) and a fibroblast cell  line (CCD-25sk) express message for adenosine receptor subtypes. RNA was isolated from  confluent monolayers of either  HUVEC or CCD-25sk cells, as described. cDNA was generated from the  isolated mRNA by reverse transcriptase and the message for the adenosine receptors was amplified by antisense primers as described. Shown is  one of two experiments yielding similar results.
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Figure 1: Endothelial cells (HUVEC) and a fibroblast cell line (CCD-25sk) express message for adenosine receptor subtypes. RNA was isolated from confluent monolayers of either HUVEC or CCD-25sk cells, as described. cDNA was generated from the isolated mRNA by reverse transcriptase and the message for the adenosine receptors was amplified by antisense primers as described. Shown is one of two experiments yielding similar results.

Mentions: To establish the profile of adenosine receptors expressed by fibroblasts and endothelial cells, we determined whether mRNA for adenosine A1, A2A, A2B, and A3 receptors was present in cultured dermal fibroblasts and HUVEC by use of reverse transcriptase–PCR. As shown in Fig. 1, message for A2A, A2B, and A3 receptors was present in both fibroblasts and HUVEC. In contrast, message for A1 receptors was expressed in HUVEC but not in fibroblasts. Results of other in vitro studies with these cells indicated that occupancy of adenosine A2 receptors, both A2A and A2B receptors, promoted migration of both fibroblasts and HUVEC into an artificial in vitro wound by a cAMP-dependent mechanism (data not shown).


Wound healing is accelerated by agonists of adenosine A2 (G alpha s-linked) receptors.

Montesinos MC, Gadangi P, Longaker M, Sung J, Levine J, Nilsen D, Reibman J, Li M, Jiang CK, Hirschhorn R, Recht PA, Ostad E, Levin RI, Cronstein BN - J. Exp. Med. (1997)

Endothelial cells  (HUVEC) and a fibroblast cell  line (CCD-25sk) express message for adenosine receptor subtypes. RNA was isolated from  confluent monolayers of either  HUVEC or CCD-25sk cells, as described. cDNA was generated from the  isolated mRNA by reverse transcriptase and the message for the adenosine receptors was amplified by antisense primers as described. Shown is  one of two experiments yielding similar results.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2199104&req=5

Figure 1: Endothelial cells (HUVEC) and a fibroblast cell line (CCD-25sk) express message for adenosine receptor subtypes. RNA was isolated from confluent monolayers of either HUVEC or CCD-25sk cells, as described. cDNA was generated from the isolated mRNA by reverse transcriptase and the message for the adenosine receptors was amplified by antisense primers as described. Shown is one of two experiments yielding similar results.
Mentions: To establish the profile of adenosine receptors expressed by fibroblasts and endothelial cells, we determined whether mRNA for adenosine A1, A2A, A2B, and A3 receptors was present in cultured dermal fibroblasts and HUVEC by use of reverse transcriptase–PCR. As shown in Fig. 1, message for A2A, A2B, and A3 receptors was present in both fibroblasts and HUVEC. In contrast, message for A1 receptors was expressed in HUVEC but not in fibroblasts. Results of other in vitro studies with these cells indicated that occupancy of adenosine A2 receptors, both A2A and A2B receptors, promoted migration of both fibroblasts and HUVEC into an artificial in vitro wound by a cAMP-dependent mechanism (data not shown).

Bottom Line: In rats rendered diabetic (streptozotocin-induced diabetes mellitus) wound healing was impaired as compared to nondiabetic rats; CGS-21680 significantly increased the rate of wound healing in both nondiabetic and diabetic rats.Indeed, the rate of wound healing in the CGS-21680-treated diabetic rats was greater than or equal to that observed in untreated normal rats.These results appear to constitute the first evidence that a small molecule, such as an adenosine receptor agonist, accelerates wound healing in both normal animals and in animals with impaired wound healing.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, New York University Medical Center, New York 10016, USA.

ABSTRACT
The complete healing of wounds is the final step in a highly regulated response to injury. Although many of the molecular mediators and cellular events of healing are known, their manipulation for the enhancement and acceleration of wound closure has not proven practical as yet. We and others have established that adenosine is a potent regulator of the inflammatory response, which is a component of wound healing. We now report that ligation of the G alpha s-linked adenosine receptors on the cells of an artificial wound dramatically alters the kinetics of wound closure. Excisional wound closure in normal, healthy mice was significantly accelerated by topical application of the specific A2A receptor agonist CGS-21680 (50% closure by day 2 in A2 receptor antagonists. In rats rendered diabetic (streptozotocin-induced diabetes mellitus) wound healing was impaired as compared to nondiabetic rats; CGS-21680 significantly increased the rate of wound healing in both nondiabetic and diabetic rats. Indeed, the rate of wound healing in the CGS-21680-treated diabetic rats was greater than or equal to that observed in untreated normal rats. These results appear to constitute the first evidence that a small molecule, such as an adenosine receptor agonist, accelerates wound healing in both normal animals and in animals with impaired wound healing.

Show MeSH
Related in: MedlinePlus