The Role of Jak3 in Skin Wound Healing
피부 상처 치유에서 Jak3의 역할
- 주제(키워드) Jak3 , skin , skin wound healing model , fibroblast , sebaceous gland
- 주제(DDC) 610
- 발행기관 아주대학교
- 지도교수 백은주
- 발행년도 2023
- 학위수여년월 2023. 8
- 학위명 석사
- 학과 및 전공 일반대학원 의학과
- 실제URI http://www.dcollection.net/handler/ajou/000000032927
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Janus kinase 3(Jak3) regulates the proliferation, differentiation, and migration of the immune system and progenitors, and controls organ morphogenesis. Jak3 has been shown as a beneficial target for the treatment of chronic skin inflammatory diseases such as psoriasis and alopecia areata. However, the detailed roles of Jak3 on the skin is not known. Therefore, this study attempted to study the function of Jak3 in the process of healing skin wounds by administering WHIp-131, a selective Jak3 inhibitor, to mouse skin wounds. To find out the role of Jak3 signaling on the skin repair and regeneration, in vivo skin wound healing model on the mouse back skin was conducted. The wound closure had occurred due to pure healing and another contraction capacity. The skin contracture is due to activated fibroblasts and myoblasts. Jak3 inhibitor significantly reduced the skin contraction rather than the healing. In addition, the thickness of the epidermis of the wound bed and the thickness of the dermal muscle layer were decreased by Jak3 inhibition. Fibroblasts from the dermis were cultured to investigate the role of fibroblasts in wound healing and contraction. As a result of administration of Jak3 inhibitor to the in vitro cultured dermal fibroblasts, a significant decrease in proliferation and migration was observed, and it was also confirmed that structure of vimentin did not exist near the nucleus but only at the end of fibroblasts, affecting motility. In addition, it was possible to confirm that isolectin B4 was used as a marker for sebaceous cells, and as a result of observing in vivo and in vitro sebaceous cells, Jak3 inhibition significantly decrease the size of regenerating sebaceous glands, but also the sebocytes. In conclusion, Jak3 signaling is involved in skin contraction and regulates fibroblast proliferation and migration through ytoskeletal changes, including vimentin. It also regulates the area of sebocytes in regenerating pilosebaceous units. In this study, isolectin B4 is suggested as a sebaceous cell marker. Also, it suggests that Jak3 inhibitors have potentials to control the contracture of wounds and to improve hair loss and acne further.
more목차
I. INTRODUCTION 1
II. MATERIALS AND METHODS 6
A. Animals 6
B. Skin wound healing model 6
C. Drug treatment (in vivo) 8
D. Cryostat section 8
E. H&E stain 8
F. Immunohistochemistry 9
G. Primary sebocyte culture 9
H. Primary skin fibroblast culture 10
I. Wound healing assay 10
J. MTT assay 11
K. Drug treatment (in vitro) 11
L. Oil red O stain 11
M. Immunocytochemistry 12
N. Western blot 12
O. Statistical analysis 12
III. RESULTS 14
A. Reduction of skin contraction by Jak3 inhibition 14
B. Effect of Jak3 inhibitor on the DMSO-induced contraction 16
C. Reduction of epidermis thickness by Jak3 inhibition 19
D. Reduction of hypodermic muscle thickness by Jak3 inhibition 21
E. Decrease of MMPs, results of α-SMA and vimentin in western blot 23
F. Decrease of cell proliferation using MTT assay 25
G. Reduced migration of fibroblasts by Jak3 inhibition 27
H. Sebaceous gland in the hair follicle stained by isolectin B4 30
I. Decrease in the area of sebocyte and the volume of sebaceous gland stained by isolectin B4 32
J. Decreased the size of primary cultured sebaceous glands by Jak3 inhibition 34
IV. DISCUSSION 36
V. REFERENCES 39
