Effect of Janus Kinase 3 Inhibitor on Sebaceous Gland Regeneration during Skin Wound Healing
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Background: Janus kinase (Jak) 3 has recently been shown as a beneficial target for the treatment of chronic inf lammatory diseases, such as psoriasis and alopecia areata. The role of Jak3 in tissue repair and remodeling is emerging. Objective: This study aimed to investigate the role of Jak3 signaling in the remodeling of the sebaceous gland (SG) during skin wound repair, and the development of in vitro SGs. Methods: Mouse skin tissue (ICR mouse) was obtained from the recovered skin eight days after a 4 mm biopsy punch wound. To observe the role of Jak3, the selective inhibitors WHI- p131 and PF06651600 was administered. Formation of in vitro SG was examined using pri- mary sebocyte cultures obtained postnatally from 3-day-old mice. Results: The data showed that SGs showed highly positive signals with anti-isolectin B4, which also used for detection of angiogenetic vessels and the basal epidermis. Isolectin B4 could be a good indicator of SGs. The Jak3 inhibitors significantly reduced the area and vol- ume of SG remodeling with reduced expression of p-Jak3. In addition, the area of cultured intact SG in vitro was significantly decreased in a concentration-dependent manner by Jak3 inhibition. Conclusion: These data showed that Jak3 signaling is a potent regulator to develop SGs. Jak3 inhibition did not decrease the number of sebocytes in SGs but decreased the area and volume of SG remodeling. Therefore, Jak3 inhibition may be a potential target for the treat- ment of SG hyperplasia and associated skin diseases.
Abstract
Background: Janus kinase (Jak) 3 has recently been shown as a beneficial target for the treatment of chronic inf lammatory diseases, such as psoriasis and alopecia areata. The role of Jak3 in tissue repair and remodeling is emerging. Objective: This study aimed to investigate the role of Jak3 signaling in the remodeling of the sebaceous gland (SG) during skin wound repair, and the development of in vitro SGs. Methods: Mouse skin tissue (ICR mouse) was obtained from the recovered skin eight days after a 4 mm biopsy punch wound. To observe the role of Jak3, the selective inhibitors WHI- p131 and PF06651600 was administered. Formation of in vitro SG was examined using pri- mary sebocyte cultures obtained postnatally from 3-day-old mice. Results: The data showed that SGs showed highly positive signals with anti-isolectin B4, which also used for detection of angiogenetic vessels and the basal epidermis. Isolectin B4 could be a good indicator of SGs. The Jak3 inhibitors significantly reduced the area and vol- ume of SG remodeling with reduced expression of p-Jak3. In addition, the area of cultured intact SG in vitro was significantly decreased in a concentration-dependent manner by Jak3 inhibition. Conclusion: These data showed that Jak3 signaling is a potent regulator to develop SGs. Jak3 inhibition did not decrease the number of sebocytes in SGs but decreased the area and volume of SG remodeling. Therefore, Jak3 inhibition may be a potential target for the treat- ment of SG hyperplasia and associated skin diseases.
참고문헌 (44)
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