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Studies of Accelerating Skin Wound Repair through Mitochondrial Energy Metabolism and Extracellular Matrix (ECM)-Mediated Cell Survival in Impaired Healing Environment

Studies of Accelerating Skin Wound Repair through Mitochondrial Energy Metabolism and Extracellular Matrix (ECM)-Mediated Cell Survival in Impaired Healing Environment
Alternative Title
손상된 치유 환경에서 미토콘드리아 에너지 대사와 세포외기질 매개 세포 생존을 통한 피부 상처 회복 촉진 연구
Seung-Hwa Woo
DGIST Authors
Seung-Hwa WooYoung-Sam LeeChang-Hun Lee
Chang-Hun Lee
Issued Date
Awarded Date
non-healing wound; skin homeostasis; skin elasticity; senescence; mitochondrial energy maintenance; fibro-blasts; adipose-derived stem cells; ageing; type II diabetes; ANT2; REP.
The skin is the first organ to protect the body from the external environment and consists of several layers including the epidermis, dermis, and subcutaneous layer. In general, the skin acts as a barrier against the external environment. When the skin is damaged, it undergoes a wound-healing process in which the damaged tissue is replaced by new tissue. This is a complex and tightly coordinated process involving many different cell types. However, if even one phase in the wound healing process is not working properly, the wound will not heal - this is called a non-healing wound. This means that even a minor injury can be the start of a non-healing wound and can increase the risk of long-term infection. The incidence of non-healing wounds tends to increase, especially as the number of elderly people and patients with metabolic diseases increases in modern society. Many approaches to understanding and accelerating wound healing are steadily emerging in the fields of medicine, tissue engineering, cell function, and genetic analysis. Here, I present studies aimed at understanding the biological events during wound healing in two types of non-healing wound models. First, I present a novel function of ANT2, a mitochondrial ADP/ATP translocase that imports ATP into mitochondria for energy homeostasis in aging. This research shows that ANT2 accelerates wound healing in aged skin, linking the maintenance of energy metabolism and skin homeostasis. Specifically, there were improvements in cell proliferation, energy homeostasis, and inflammation in aging, showing positive effects on the wound healing environment. Next, I describe a novel therapeutic effect of RGD-modified elastin-like polypeptide (RGD-ELP, REP), as a scaffold for stem cell delivery to type II diabetic wounds. REP accelerated wound healing and improved skin elasticity by regulating angiogenesis in diabetic skin. By presenting previously unreported studies to improve wound healing in aging and diabetic models, this thesis provides new biological perspectives based on mitochondrial energy metabolism and extracellular matrix (ECM)-mediated cell survival in impaired healing environments.|피부는 외부 환경으로부터 신체를 보호하는 첫 번째 기관으로 표피, 진피, 피하지방층을 포함한 여러 층으로 구성되어 있다. 피부에 상처가 난 경우 손상된 조직은 지혈, 염증, 증식, 성숙 단계를 따라 새로운 조직으로 대체하는 상처 치유 과정을 거친다. 이 과정은 다양한 세포 유형에 의해 복잡하고 긴밀하게 조율되며, 한 단계라도 적절히 진행되지 않는 경우 상처 치유가 지연된다. 즉, 경미한 부상도 치유되지 않는 상처의 시작이 될 수 있으며 장기 감염의 위험이 높아질 수 있다. 특히 현대 사회에서 노인과 대사성 질환 환자의 수가 증가함에 따라 상처 회복 지연율이 증가하고 있다. 의학, 조직 공학, 생물학 분야에서 상처 치유를 이해하고 가속화하기 위한 다양한 접근법이 꾸준히 등장하고 있으며, 논문에서는 상처 지연 모델에서 상처 치유에 필수적인 생물학적 요인을 탐구한 연구들을 소개한다. 먼저, 에너지 항상성을 위해 미토콘드리아로 ATP를 가져오는 미토콘드리아 ADP/ATP trans-locase2 (ANT2)의 새로운 기능을 소개한다. ANT2는 노화 피부에서 세포 증식, 에너지 항상성, 염증 등을 개선하여 상처 치유를 가속화했다. 이 연구는 에너지 대사와 피부 항상성을 연결시킨다는 점에 의의가 있다. 다음으로, 제2형 당뇨병 상처에 줄기세포를 전달하기 위한 스캐폴드로써 REP의 새로운 치료 효과에 대해 소개한다. REP는 당뇨병 피부의 혈관신생을 조절하여 상처 치유를 촉진했고 피부 탄력을 개선했다. 따라서, 노화 및 당뇨병 모델에서 이전에 보고되지 않은 상처 치유 개선 방안에 대한 연구들을 제시함으로써 손상된 치유 환경에서 미토콘드리아 에너지 대사와 세포외기질(ECM) 매개 세포 생존을 기반으로 한 새로운 생물학적 관점을 제공한다.
Table Of Contents
I. Introduction and background study 1
1.1 Organization of thesis 1
1.2 Skin 3
1.2.1 Function of skin 3
1.2.2 Epidermis 3
1.2.3 Dermis 4
1.3 Wound healing process 6
1.3.1 The overall wound healing process 6
1.3.2 Hemostasis 6
1.3.3 Inflammation 7
1.3.4 Proliferation 7
1.3.5 Remodeling 8
1.4 Non-healing wound 11
1.4.1 Acute wound and non-healing (chronic) wound 11
1.4.2 Skin in aging 11
1.4.3 Skin in diabetes 12
1.5 Wound therapy 13
1.5.1 Medical treatment 13
1.5.2 Biological perspective 14
II. ANT2 accelerates cutaneous wound healing in aged skin via regulating energy homeostasis and inflammation 17
2.1 Introduction 17
2.2 Materials and methods 20
2.3 Results 36
2.4 Discussion 93
2.5 Acknowledgment 98
III. Engineered elastin-like polypeptide accelerates cutaneous wound healing with improving skin elasticity in type II diabetic mellitus 99
3.1 Introduction 99
3.2 Materials and methods 102
3.3 Results 106
3.4 Discussion 121
3.5 Acknowledgment 123
IV. Conclusion and future work 124
References 126
국문 요약 136
Department of New Biology
Related Researcher
  • 이영삼 Lee, Young-Sam 뉴바이올로지학과
  • Research Interests DNA replication and repair; Restoration of cellular senescence; Structural and functional relationship of proteins
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Department of New Biology Theses Ph.D.


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