간세포증식인자
Hepatocyte growth factor간세포증식인자(HGF) 또는 산란인자(SF)는 파라크린 세포증식, 운동성 및 형태유발인자이다.간엽세포와 표적에서 분비되며 주로 상피세포와 내피세포에 작용하지만 조혈성 전구세포와 T세포에도 작용한다.그것은 배아 장기 발달, 특히 근생성, 성인 장기 재생, 상처 [5]치유에 중요한 역할을 하는 것으로 나타났다.
기능.
간세포증식인자는 원생 c-Met 수용체에 결합 [6][7]후 티로신인산화효소 시그널링을 활성화함으로써 세포성장, 세포운동성 및 형태형성을 조절한다.간세포증식인자는 간엽세포에서 분비되며 주로 상피기원의 세포에서 다기능성 사이토카인으로 작용한다.유사분열 발생, 세포 운동성, 매트릭스 침입을 자극하는 능력은 혈관신생, 종양신생, 조직재생에 [8]중추적인 역할을 한다.
구조.
단일 불활성 폴리펩타이드로 분비되며, 세린 단백질 분해 효소에 의해 69-kDa 알파사슬과 34-kDa 베타사슬로 분해된다.알파 사슬과 베타 사슬 사이의 디술피드 결합은 활성, 헤테로다이머 분자를 생성한다.단백질은 S1 펩티드가수분해효소의 플라스미노겐 서브패밀리에 속하지만 단백질 분해효소 활성은 [8]검출되지 않는다.
임상적 의의
심근세포의 인간 HGF 플라스미드 DNA 치료는 심근경색 [9][10]후 심장에 발생하는 손상에 대한 치료뿐만 아니라 관상동맥 질환의 잠재적 치료법으로서 검토되고 있다.HGF는 상피세포, 내피세포 및 조혈성 전구세포에 대한 HGF의 잘 알려진 영향과 더불어 심장조직에 대한 T세포의 화학축성을 조절한다.T세포에서 발현되는 c-Met에 의한 HGF의 결합은 c-Met, CXCR3, CCR4의 상향 조절을 유발하여 심장 [11]조직으로 이동하는 능력을 주입한다.HGF는 또한 [12]허혈손상에서의 혈관신생을 촉진한다.HGF는 치쿤구냐 바이러스 유발 관절통의 만성 예후 지표로서 더욱 중요한 역할을 할 수 있다.높은 HGF 수준은 높은 [13]회복률과 관련이 있습니다.
유방 내 HGF의 과도한 국소적 발현은 [14]대유행에 관여하고 있다.HGF는 또한 정상적인 유선 [15][16]발달에 중요하다.
HGF는 폐, 췌장, 갑상선, 대장, 그리고 [17][18][19]유방을 포함한 다양한 암에 관련되어 있다.
HGF의 발현 증가는 구강 점막 [20]조직에서 분리된 섬유아세포의 향상된 흉터 없는 상처 치유 능력과 관련이 있다.
순환 혈장 수준
진행성 심부전 환자의 혈장은 HGF의 수치가 증가하며, 이는 부정적인 [21][22]예후와 높은 사망 위험과 관련이 있다.또한 순환하는 HGF는 [23]고혈압 환자의 중증도에 대한 예후 지표로 확인되었다.순환하는 HGF는 또한 장염의 [24]급성 국면에 대한 조숙한 바이오마커로 제안되었다.
약동학
정맥주사로 투여된 외인성 HGF는 간에 의해 순환에서 빠르게 제거되며, 반감기는 약 [25][26][27][28]4분이다.
변조기
Dihexa는 HGF에 직접 결합하고 수용체인 [29]c-Met을 활성화하는 능력을 강화하는 구강 활성, 중앙 침투성 소분자 화합물이다.그것은 신경 발생의 강력한 유도제이며 알츠하이머병과 [30][31]파킨슨병의 잠재적 치료법을 위해 연구되고 있다.
상호 작용
간세포 성장 인자는 HGF 수용체(HGFR)[6][32][33]로 식별되는 c-Met 종양 유전자의 단백질 생성물과 상호작용하는 것으로 나타났다.간세포증식인자배위자의 동시발현에 의한 Met/HGFR 수용체 단백질의 과잉발현과 Met/HGFR의 자가분비 활성화가 모두 [34][35]발암에 관여하고 있다.간세포증식인자는 황산글리코사미노글리칸 헤파란 황산염 및 데마난 [36][37]황산염과 상호작용한다.헤파란 황산염과의 상호작용을 통해 간세포 성장 인자가 세포 분열 및 [36][38]세포 이동으로 이어지는 세포 내 신호를 전달할 수 있는 c-Met과 복합체를 형성할 수 있습니다.
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레퍼런스
- ^ a b c GRCh38: 앙상블 릴리즈 89: ENSG000019991 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리즈 89: ENSMUSG000028864 - 앙상블, 2017년 5월
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추가 정보
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