¹æ»ç¼±Á¶»çµÈ Æó¿¡¼ Melatonin¿¡ ÀÇÇÑ TGF-¥â1 ¹ßÇöÀÇ º¯È
The Change of Transforming Growth Factor ¥â1 (TGF-¥â1) Expression by Melatonin in Irradiated Lung
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À强¼ø/Jang SS
ÃÖÀϺÀ/Choi IB
KMID : 0859320050230030161
Abstract
¸ñ Àû: °·ÂÇÑ Ç×»êÈ È¿°ú¸¦ Áö´Ñ melatoninÀ» ÀüóġÇÏ¿´À» ¶§ ¹æ»ç¼±À¯µµ¼º ¼¶À¯Áõ °úÁ¤¿¡¼ Áß¿äÇÑ »çÀÌÅäÄ«ÀÎÀÎ TGF-¥â1ÀÇ º¯ÈµÈ ¹ßÇö¾ç»óÀ» ¸¶¿ì½º Æó¿¡¼ ¿¬±¸ÇÏ¿´´Ù.
´ë»ó ¹× ¹æ¹ý: C57BL/6 ¸¶¿ì½º¸¦ ½ÇÇ豺¿¡ µû¶ó ¼¼ ±º(´ëÁ¶±º, ¹æ»ç¼±Á¶»ç ´Üµ¶±º, melatonin Àüóġ±º(¹æ»ç¼±Á¶»ç 1½Ã°£ Àü¿¡ 300 mg/kg º¹°ÁÖ»ç))À¸·Î ºÐ·ùÇÏ°í ¾çÃø Èä°û¿¡ 12 GyÀÇ ¼±·®À» ´ÜÀÏÁ¶»çÇÏ¿´´Ù. ¹æ»ç¼±Á¶»ç ÈÄ 2ÁÖ¿Í 4ÁÖÀÇ ÆóÁ¶Á÷¿¡¼ TGF-¥â1 mRNA ¹ßÇö¼öÁØÀ» ÃøÁ¤Çϱâ À§ÇØ semiquantitive RT-PCR¸¦ ½ÃÇàÇÏ¿´°í, TGF-¥â1 protein ¹ßÇöÀÇ ¼öÁØ°ú À§Ä¡¸¦ º¸±â À§ÇØ ¸é¿ªÁ¶Á÷ÈÇп°»öÀ» ½ÃÇàÇÏ¿´´Ù.
°á °ú: 2ÁÖ ÈÄ¿¡ ÃøÁ¤µÈ mRNA ¹ßÇöÀº ¹æ»ç¼±Á¶»ç ´Üµ¶±º°ú melatonin Àüóġ±º¿¡¼ °¢°¢ ´ëÁ¶±ºÀÇ 1.92¹è¿Í 1.80¹è Áõ°¡µÈ ¼öÁØÀ» º¸¿´°í(p=0.064), 4ÁÖ ÈÄ¿¡´Â °¢°¢ 2.38¹è¿Í 1.94¹è ¼öÁØÀÇ Áõ°¡µÈ ¹ßÇöÀ» º¸¿´´Ù(p= 0.004). TGF-¥â1 proteinÀÇ ¹ßÇöÀº Á¶Á÷º´¸®ÇÐÀûÀ¸·Î ¹æ»ç¼±¼Õ»ó ¿µ¿ª¿¡¼ ÁÖ·Î °üÂûµÇ¾ú´Âµ¥ ÆóÆ÷ ´ë½Ä¼¼Æ÷¿Í ÆóÆ÷º®ÀÇ »óÇǼ¼Æ÷µéÀÌ ÁÖ¿ä ±Ù¿øÀ̾ú´Ù. ¹ßÇö¼öÁØÀº 2ÁÖ¿Í 4ÁÖ ÈÄ¿¡ °¢°¢ 15.8% vs 16.9% (p=0.565), ±×¸®°í 36.1% vs 25.7% (p=0.009)À̾ú´Ù.
°á ·Ð: Melatonin Àüóġ·Î ¹æ»ç¼±Á¶»ç¿¡ ÀÇÇÑ TGF-¥â1 mRNA¿Í proteinÀÇ ¹ßÇöÀÌ 4ÁÖ ÈÄ¿¡ À¯ÀÇÇÏ°Ô °¨¼ÒµÊÀ» °üÂûÇÏ¿´´Ù. µû¶ó¼ ¹æ»ç¼±À¸·Î ÀÎÇÑ Æó¼Õ»ó ½Ã¿¡ Ç×¼¶À¯Áõ ¾à¹°·ÎÀÇ »ç¿ë°¡´É¼ºÀ» È®ÀÎÇÏ¿´´Ù.
Purpose: The changed expressions of TGF-¥â1, as a key cytokine in the fibrotic process, due to melatonin with potent antioxidative effects, were investigated in the irradiated lung using fibrosis-sensitive C57BL/6 mice.
Materials and Methods: Female C57BL/6 mice were divided into control irradiation-only, and melatonin (300 mg/kg i.p. 1 hr before irradiation) pretreatment groups. The thoraces of the mice were irradiated with a single dose of 12 Gy. The mRNA expressions of TGF-¥â1 in the lung tissue 2 and 4 weeks after irradiation were quantified using semiquantitive RT-PCR, and the cellular origin and expression levels of TGF-¥â1 protein were identified using immunohistochemical staining.
Results: The relative mRNA expression levels in the irradiation-only and melatonin pretreatment groups 2 and 4 weeks after irradiation were 1.92- and 1.80-fold (p=0.064) and 2.38- and 1.94-fold (p=0.004) increased, respectively compared to those in the control group. Increased expressions of TGF-¥â1 protein were prominently detected in regions of histopathological radiation injury, with alveolar macrophages and septal epithelial cells serving as important sources of TGF-¥â1 expression. At 2 and 4 weeks after irradiation, the expression levels of protein were 15.8% vs. 16.9% (p=0.565) and 36.1% vs. 25.7% (p=0.009), respectively.
Conclusion: The mRNA and protein expressions of TGF-¥â1 in the lung tissue following thoracic irradiation with 12 Gy were significantly decreased by melatonin pretreatment at 4 weeks. These results indicate that melatonin may have a possible application as an antifibrotic agent in radiation-induced lung injury.
Å°¿öµå
Melatonin; TGF-¥â1; ¹æ»ç¼± ¼¶À¯Áõ; Melatonin; Radiation; Fibrosis
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