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Erschienen in: International Journal of Legal Medicine 4/2011

01.07.2011 | Original Article

Time-dependent expression and distribution of monoacylglycerol lipase during the skin-incised wound healing in mice

verfasst von: Wen-Xiang Ma, Tian-Shui Yu, Yan-Yan Fan, Shu-Tao Zhang, Peng Ren, Shuai-Bo Wang, Rui Zhao, Jing-Bo Pi, Da-Wei Guan

Erschienen in: International Journal of Legal Medicine | Ausgabe 4/2011

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Abstract

The study investigated the expression of monoacylglycerol lipase (MGL) during the skin-incised wound healing in mice and applicability of the time-dependent expression of MGL to wound age determination by immunofluorescent staining, Western blotting, and real-time PCR. Furthermore, cell types were identified by double immunofluorescence. A total of 45 BALB/c male mice were used in this study. After a 1.5-cm-long incision in the central dorsum skin, mice were killed at intervals ranging from 6 h to 14 days, followed by the sampling of wound margin. In the control, there was a low-level expression of MGL in the epidermis, hair follicles, and glandulae sebaceae. In the injured skin, MGL immunoreactivity was mainly detected in the neutrophils, macrophages, and myofibroblasts. Morphometrically, the average ratios of MGL-positive cells were more than 50% at 5 and 7 days post-wounding, whereas it was <50% at the other posttraumatic intervals. By Western blotting analysis, the average ratio of MGL protein expression was highest at 5 days after injury, which had a ratio of >2.30. Similarly, the relative quantity of MGL mRNA expression maximized at posttraumatic 5 days in comparison with control as detected by real-time PCR, with an average ratio of >2.54. In conclusion, MGL expression is detected in neutrophils, macrophages, and myofibroblasts and significantly up-regulated, suggesting that it may play roles in response to inflammation during skin-incised wound healing. From the viewpoint of forensic pathology, MGL detection is applicable to skin wound age determination.
Literatur
1.
Zurück zum Zitat Marrs W, Stella N (2009) Measuring endocannabinoid hydrolysis: refining our tools and understanding. AAPS J 11:307–311PubMedCrossRef Marrs W, Stella N (2009) Measuring endocannabinoid hydrolysis: refining our tools and understanding. AAPS J 11:307–311PubMedCrossRef
2.
Zurück zum Zitat Duncan M, Thomas AD, Cluny NL, Patel A, Patel KD, Lutz B, Piomelli D, Alexander SP, Sharkey KA (2008) Distribution and function of monoacylglycerol lipase in the gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol 295:G1255–G1265PubMedCrossRef Duncan M, Thomas AD, Cluny NL, Patel A, Patel KD, Lutz B, Piomelli D, Alexander SP, Sharkey KA (2008) Distribution and function of monoacylglycerol lipase in the gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol 295:G1255–G1265PubMedCrossRef
3.
Zurück zum Zitat Puffenbarger RA (2005) Molecular biology of the enzymes that degrade endocannabinoids. Curr Drug Targets CNS Neurol Disord 4:625–631PubMedCrossRef Puffenbarger RA (2005) Molecular biology of the enzymes that degrade endocannabinoids. Curr Drug Targets CNS Neurol Disord 4:625–631PubMedCrossRef
4.
Zurück zum Zitat Karlsson M, Reue K, Xia YR, Lusis AJ, Langin D, Tornqvist H, Holm C (2001) Exon–intron organization and chromosomal localization of the mouse monoglyceride lipase gene. Gene 272:11–18PubMedCrossRef Karlsson M, Reue K, Xia YR, Lusis AJ, Langin D, Tornqvist H, Holm C (2001) Exon–intron organization and chromosomal localization of the mouse monoglyceride lipase gene. Gene 272:11–18PubMedCrossRef
5.
Zurück zum Zitat Blankman JL, Simon GM, Cravatt BF (2007) A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol. Chem Biol 14:1347–1356PubMedCrossRef Blankman JL, Simon GM, Cravatt BF (2007) A comprehensive profile of brain enzymes that hydrolyze the endocannabinoid 2-arachidonoylglycerol. Chem Biol 14:1347–1356PubMedCrossRef
7.
Zurück zum Zitat Guan DW, Ohshima T, Kondo T (2000) Immunohistochemical study on Fas and Fas ligand in skin wound healing. Histochem J 32:85–91PubMedCrossRef Guan DW, Ohshima T, Kondo T (2000) Immunohistochemical study on Fas and Fas ligand in skin wound healing. Histochem J 32:85–91PubMedCrossRef
8.
Zurück zum Zitat Kondo T, Ohshima T (1996) The dynamics of inflammatory cytokines in the healing process of mouse skin wound: a preliminary study for possible wound age determination. Int J Leg Med 108:231–267CrossRef Kondo T, Ohshima T (1996) The dynamics of inflammatory cytokines in the healing process of mouse skin wound: a preliminary study for possible wound age determination. Int J Leg Med 108:231–267CrossRef
9.
Zurück zum Zitat Dreßler J, Bachmann L, Kasper M, Hauck JG, Müller E (1997) Time dependence of the expression ICAM (CD-54) in human skin wound. Int J Leg Med 110:299–304CrossRef Dreßler J, Bachmann L, Kasper M, Hauck JG, Müller E (1997) Time dependence of the expression ICAM (CD-54) in human skin wound. Int J Leg Med 110:299–304CrossRef
10.
Zurück zum Zitat Hayashi T, Ishida Y, Kimura A, Takayasu T, Eisenmenger W, Kondo T (2004) Forensic application of VEGF expression to skin wound age determination. Int J Leg Med 118:320–325CrossRef Hayashi T, Ishida Y, Kimura A, Takayasu T, Eisenmenger W, Kondo T (2004) Forensic application of VEGF expression to skin wound age determination. Int J Leg Med 118:320–325CrossRef
11.
Zurück zum Zitat Kondo T, Ohshima T, Eisenmenger W (1999) Immunohistochemical and morphometrical study on the temporal expression of interleukin-1α(IL-1α) in human skin wounds for forensic wound age determination. Int J Leg Med 112:249–252CrossRef Kondo T, Ohshima T, Eisenmenger W (1999) Immunohistochemical and morphometrical study on the temporal expression of interleukin-1α(IL-1α) in human skin wounds for forensic wound age determination. Int J Leg Med 112:249–252CrossRef
12.
Zurück zum Zitat Kondo T, Ohshima T, Mori R, Guan DW, Ohshima K, Eisenmenger W (2002) Immunohistochemical detection of chemokines in human skin wounds and its application to wound age determination. Int J Leg Med 116:87–91CrossRef Kondo T, Ohshima T, Mori R, Guan DW, Ohshima K, Eisenmenger W (2002) Immunohistochemical detection of chemokines in human skin wounds and its application to wound age determination. Int J Leg Med 116:87–91CrossRef
13.
Zurück zum Zitat Dinh TP, Carpenter D, Leslie FM, Freund TF, Katona I, Sensi SL, Kathuria S, Piomelli D (2002) Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci USA 99:10819–10824PubMedCrossRef Dinh TP, Carpenter D, Leslie FM, Freund TF, Katona I, Sensi SL, Kathuria S, Piomelli D (2002) Brain monoglyceride lipase participating in endocannabinoid inactivation. Proc Natl Acad Sci USA 99:10819–10824PubMedCrossRef
14.
Zurück zum Zitat Gulyas AI, Cravatt BF, Bracey MH, Dinh TP, Piomelli D, Boscia F, Freund TF (2004) Segregation of two endocannabinoid-hydrolyzing enzymes into pre- and postsynaptic compartments in the rat hippocampus, cerebellum and amygdala. Eur J Neurosci 20:441–458PubMedCrossRef Gulyas AI, Cravatt BF, Bracey MH, Dinh TP, Piomelli D, Boscia F, Freund TF (2004) Segregation of two endocannabinoid-hydrolyzing enzymes into pre- and postsynaptic compartments in the rat hippocampus, cerebellum and amygdala. Eur J Neurosci 20:441–458PubMedCrossRef
15.
Zurück zum Zitat Comelli F, Giagnoni G, Bettoni I, Colleoni M, Costa B (2007) The inhibition of monoacylglycerol lipase by URB602 showed an anti-inflammatory and anti-nociceptive effect in a murine model of acute inflammation. Br J Pharmacol 152:787–794PubMedCrossRef Comelli F, Giagnoni G, Bettoni I, Colleoni M, Costa B (2007) The inhibition of monoacylglycerol lipase by URB602 showed an anti-inflammatory and anti-nociceptive effect in a murine model of acute inflammation. Br J Pharmacol 152:787–794PubMedCrossRef
16.
Zurück zum Zitat Jhaveri MD, Richardson D, Chapman V (2007) Endocannabinoid metabolism and uptake: novel targets for neuropathic and inflammatory pain. Br J Pharmacol 152:624–632PubMedCrossRef Jhaveri MD, Richardson D, Chapman V (2007) Endocannabinoid metabolism and uptake: novel targets for neuropathic and inflammatory pain. Br J Pharmacol 152:624–632PubMedCrossRef
17.
Zurück zum Zitat Hohmann AG, Suplita RL, Bolton NM, Neely MH, Fegley D, Mangieri R, Krey JF, Walker JM, Holmes PV, Crystal JD, Duranti A, Tontini A, Mor M, Tarzia G, Piomelli D (2005) An endocannabinoid mechanism for stress-induced analgesia. Nature 435:1108–1112PubMedCrossRef Hohmann AG, Suplita RL, Bolton NM, Neely MH, Fegley D, Mangieri R, Krey JF, Walker JM, Holmes PV, Crystal JD, Duranti A, Tontini A, Mor M, Tarzia G, Piomelli D (2005) An endocannabinoid mechanism for stress-induced analgesia. Nature 435:1108–1112PubMedCrossRef
18.
Zurück zum Zitat Desroches J, Guindon J, Lambert C, Beaulieu P (2008) Modulation of the anti-nociceptive effects of 2-arachidonoylglycerol by peripherally administered FAAH and MGL inhibitors in a neuropathic pain model. Br J Pharmacol 155:913–924PubMedCrossRef Desroches J, Guindon J, Lambert C, Beaulieu P (2008) Modulation of the anti-nociceptive effects of 2-arachidonoylglycerol by peripherally administered FAAH and MGL inhibitors in a neuropathic pain model. Br J Pharmacol 155:913–924PubMedCrossRef
19.
Zurück zum Zitat McPartland JM (2008) Expression of the endocannabinoid system in fibroblasts and myofascial tissues. J Bodyw Mov Ther 12:169–182PubMedCrossRef McPartland JM (2008) Expression of the endocannabinoid system in fibroblasts and myofascial tissues. J Bodyw Mov Ther 12:169–182PubMedCrossRef
20.
21.
Zurück zum Zitat Mori R, Kondo T, Nishie T, Ohshima T, Asano M (2004) Impairment of skin wound healing in beta-1,4-galactosyltransferase-deficient mice with reduced leukocyte recruitment. Am J Pathol 164:1303–1314PubMedCrossRef Mori R, Kondo T, Nishie T, Ohshima T, Asano M (2004) Impairment of skin wound healing in beta-1,4-galactosyltransferase-deficient mice with reduced leukocyte recruitment. Am J Pathol 164:1303–1314PubMedCrossRef
22.
Zurück zum Zitat Oka S, Wakui J, Ikeda S, Yanagimoto S, Kishimoto S, Gokoh M, Nasui M, Sugiura T (2006) Involvement of the cannabinoid CB2 receptor and its endogenous ligand 2-arachidonoylglycerol in oxazolone-induced contact dermatitis in mice. J Immunol 177:8796–8805PubMed Oka S, Wakui J, Ikeda S, Yanagimoto S, Kishimoto S, Gokoh M, Nasui M, Sugiura T (2006) Involvement of the cannabinoid CB2 receptor and its endogenous ligand 2-arachidonoylglycerol in oxazolone-induced contact dermatitis in mice. J Immunol 177:8796–8805PubMed
23.
Zurück zum Zitat Facchinetti F, Del Giudice E, Furegato S, Passarotto M, Leon A (2003) Cannabinoids ablate release of TNF alpha in rat microglial cells stimulated with lypopolysaccharide. Glia 41:161–168PubMedCrossRef Facchinetti F, Del Giudice E, Furegato S, Passarotto M, Leon A (2003) Cannabinoids ablate release of TNF alpha in rat microglial cells stimulated with lypopolysaccharide. Glia 41:161–168PubMedCrossRef
24.
Zurück zum Zitat Jordà MA, Verbakel SE, Valk PJ, Vankan-Berkhoudt YV, Maccarrone M, Finazzi-Agrò A, Löwenberg B, Delwel R (2002) Hematopoietic cells expressing the peripheral cannabinoid receptor migrate in response to the endocannabinoid 2-arachidonoylglycerol. Blood 99:2786–2793PubMedCrossRef Jordà MA, Verbakel SE, Valk PJ, Vankan-Berkhoudt YV, Maccarrone M, Finazzi-Agrò A, Löwenberg B, Delwel R (2002) Hematopoietic cells expressing the peripheral cannabinoid receptor migrate in response to the endocannabinoid 2-arachidonoylglycerol. Blood 99:2786–2793PubMedCrossRef
25.
Zurück zum Zitat Yu TS, Cheng ZH, Li LQ, Zhao R, Fan YY, Du Y, Ma WX, Guan DW (2010) The cannabinoid receptor type 2 is time-dependently expressed during skeletal muscle wound healing in rats. Int J Leg Med 124:397–404CrossRef Yu TS, Cheng ZH, Li LQ, Zhao R, Fan YY, Du Y, Ma WX, Guan DW (2010) The cannabinoid receptor type 2 is time-dependently expressed during skeletal muscle wound healing in rats. Int J Leg Med 124:397–404CrossRef
26.
Zurück zum Zitat Di Marzo V, Bisogno T, De Petrocellis L, Melck D, Orlando P, Wagner JA, Kunos G (1999) Biosynthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in circulating and tumoral macrophages. Eur J Biochem 264:258–267PubMedCrossRef Di Marzo V, Bisogno T, De Petrocellis L, Melck D, Orlando P, Wagner JA, Kunos G (1999) Biosynthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in circulating and tumoral macrophages. Eur J Biochem 264:258–267PubMedCrossRef
27.
Zurück zum Zitat Walter L, Dinh T, Stella N (2004) ATP induces a rapid and pronounced increase in 2-arachidonoylglycerol production by astrocytes, a response limited by monoacylglycerol lipase. J Neurosci 24:8068–8074PubMedCrossRef Walter L, Dinh T, Stella N (2004) ATP induces a rapid and pronounced increase in 2-arachidonoylglycerol production by astrocytes, a response limited by monoacylglycerol lipase. J Neurosci 24:8068–8074PubMedCrossRef
28.
Zurück zum Zitat Cecchi R (2010) Estimating wound age: looking into the future. Int J Leg Med 124:523–536CrossRef Cecchi R (2010) Estimating wound age: looking into the future. Int J Leg Med 124:523–536CrossRef
29.
Zurück zum Zitat Kagawa S, Matsuo A, Yagi Y, Ikematsu K, Tsuda R, Nakasono I (2009) The time-course analysis of gene expression during wound healing in mouse skin. Leg Med (Tokyo) 11:70–75 Kagawa S, Matsuo A, Yagi Y, Ikematsu K, Tsuda R, Nakasono I (2009) The time-course analysis of gene expression during wound healing in mouse skin. Leg Med (Tokyo) 11:70–75
30.
Zurück zum Zitat Sun JH, Wang YY, Zhang L, Gao CR, Zhang LZ, Guo Z (2010) Time-dependent expression of skeletal muscle troponin I mRNA in the contused skeletal muscle of rats: a possible marker for wound age estimation. Int J Leg Med 124:27–33CrossRef Sun JH, Wang YY, Zhang L, Gao CR, Zhang LZ, Guo Z (2010) Time-dependent expression of skeletal muscle troponin I mRNA in the contused skeletal muscle of rats: a possible marker for wound age estimation. Int J Leg Med 124:27–33CrossRef
31.
Zurück zum Zitat Ohshima T, Sato Y (1998) Time-dependent expression of interleukin-10 (IL-10) mRNA during the early phase of skin wound healing as a possible indicator of wound vitality. Int J Leg Med 111:251–255CrossRef Ohshima T, Sato Y (1998) Time-dependent expression of interleukin-10 (IL-10) mRNA during the early phase of skin wound healing as a possible indicator of wound vitality. Int J Leg Med 111:251–255CrossRef
32.
Zurück zum Zitat Bai R, Wan L, Shi M (2008) The time-dependent expressions of IL-1beta, COX-2, MCP-1 mRNA in skin wounds of rabbits. Forensic Sci Int 175:193–197PubMedCrossRef Bai R, Wan L, Shi M (2008) The time-dependent expressions of IL-1beta, COX-2, MCP-1 mRNA in skin wounds of rabbits. Forensic Sci Int 175:193–197PubMedCrossRef
Metadaten
Titel
Time-dependent expression and distribution of monoacylglycerol lipase during the skin-incised wound healing in mice
verfasst von
Wen-Xiang Ma
Tian-Shui Yu
Yan-Yan Fan
Shu-Tao Zhang
Peng Ren
Shuai-Bo Wang
Rui Zhao
Jing-Bo Pi
Da-Wei Guan
Publikationsdatum
01.07.2011
Verlag
Springer-Verlag
Erschienen in
International Journal of Legal Medicine / Ausgabe 4/2011
Print ISSN: 0937-9827
Elektronische ISSN: 1437-1596
DOI
https://doi.org/10.1007/s00414-011-0567-4

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