Tissue kallikrein in cardiovascular, cerebrovascular and renal diseases and skin wound healing.
Tissue kallikrein (KLK1) processes low-molecular weight kininogen to produce vasoactive kinins, which exert biological functions via kinin receptor signaling. Using various delivery approaches, we have demonstrated that tissue kallikrein through kinin B2 receptor signaling exhibits a wide spectrum of beneficial effects by reducing cardiac and renal injuries, restenosis and ischemic stroke, and by promoting angiogenesis and skin wound healing, independent of blood pressure reduction. Protection by tissue kallikrein in oxidative organ damage is attributed to the inhibition of apoptosis, inflammation, hypertrophy and fibrosis. Tissue kallikrein also enhances neovascularization in ischemic heart and limb. Moreover, tissue kallikrein/kinin infusion not only prevents but also reverses kidney injury, inflammation and fibrosis in salt-induced hypertensive rats. Furthermore, there is a wide time window for kallikrein administration in protection against ischemic brain infarction, as delayed kallikrein infusion for 24 h after cerebral ischemia in rats is effective in reducing neurological deficits, infarct size, apoptosis and inflammation. Importantly, in the clinical setting, human tissue kallikrein has been proven to be effective in the treatment of patients with acute brain infarction when injected within 48 h after stroke onset. Finally, kallikrein promotes skin wound healing and keratinocyte migration by direct activation of protease-activated receptor 1.
Chao
Julie
J
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, 29425, USA. chaoj@musc.edu
Shen
Bo
B
Gao
Lin
L
Xia
Chun-Fang
CF
Bledsoe
Grant
G
Chao
Lee
L
D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D002561:Cerebrovascular Disorders / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism* / Q000517:prevention & control; D012867:Skin / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D020840:Tissue Kallikreins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D014945:Wound Healing
D020840:Tissue Kallikreins