Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adapalene is a new naphthoic acid derivative with strong retinoid agonistic pharmacological properties. We propose that adapalene might contribute to the wound repairing process as is detected with retinoids. In this controlled study, the effects of topical adapalene, tretinoin and collagenase on full-thickness wound healing were compared in an animal model. Thirty-two adult male Wistar-Albino rats were used in the study. Two circular, full-thickness wounds were made for each animal with a standard 8-mm punch biopsy, on both sides of the midline on the back. No treatment was given to Group I rats (n:8) which comprised the control group. Tretinoin cream (0.1%) was applied topically in Group II (n:8), adapalene gel (0.1%) in Group III (n:8), and collagenase ointment in Group IV (n:8) once daily. On day 7, the wounds were photographed to measure the wound surface area. The wounds on the left side of each animal were excised on day 7, for histopathologic and biochemical examination. The treatments were continued for the right side wounds up to 14 days when the same procedure was repeated. In Group II, a significant decrease in hydroxylproline (HP) levels was detected at day 7 (p = 0.018), and an increase at day 14 (p = 0.002) compared to the control group. HP results revealed no difference either in Group III nor in Group IV versus control at day 7 or 14. However, findings of improved healing were more prominent in Groups II and III than the other groups in histopathologic examination. In conclusion, tretinoin and adapalene contributed to the wound healing process resulting in an enhancement of collagen production, angiogenesis and granulation tissue formation.
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PMID:Comparison of the effects of tretinoin, adapalene and collagenase in an experimental model of wound healing. 1187 10

Keloids are skin abnormalities that are characterized by excessive deposition of collagen bundles in the dermis. Patients with keloids complain not only about their cosmetic appearance, but also about continuous itching and/or tenderness associated with chronic inflammation. Degradation of extracellular matrix (ECM) may be upregulated, associated with the expansion of keloids into circumferential skin, and high metabolic activity of keloid tissues may be due to increased matrix metalloproteinase (MMP) activity. Based on these hypotheses, we examined differences in expression of MMP-1, MMP-8, and MMP-13 between keloid-derived and normal dermal fibroblasts. Since retinoids are potent inhibitors of MMPs in the treatment of photoaged skin and cancers, we also examined whether or not tretinoin affects MMP expression of keloid-derived fibroblasts. The results of real-time polymerase chain reaction and ELISA demonstrated significant upregulation of MMP-13 and significant downregulation of MMP-1 and MMP-8 in keloid-derived fibroblasts, at both mRNA and protein levels. MMP-1 mRNA expression in the control group was significantly upregulated after the addition of tretinoin, whereas no significant change was observed in the keloid group. MMP-8 mRNA expression in the control group was significantly upregulated by tretinoin, with the peak at 12 h, while no significant change was observed in the keloid-derived fibroblasts. In contrast, the remarkably elevated MMP-13 mRNA expression in the keloid group was significantly suppressed, with the peak suppression at 12 h after addition of tretinoin, while MMP-13 mRNA expression in the control group was not significantly changed. The decrease in MMP-1 and MMP-8 may contribute to accumulation of type I and type III collagen in keloid tissues, and this mechanism may be modulated by molecular interaction with MMP-13. Tretinoin appeared to reverse the abnormal expression profile of MMPs in keloid-derived fibroblasts, such as markedly elevated expression of MMP-13, partly through inactivation of AP-1 pathway. The present results suggest that tretinoin may be clinically useful to improve the chronic inflammation seen in keloids and prevent expansion of keloid tissues into circumferential normal skin.
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PMID:Tretinoin reverses upregulation of matrix metalloproteinase-13 in human keloid-derived fibroblasts. 1475 22