Liver cirrhosis is reverted by urokinase-type plasminogen activator gene therapy.
Liver cirrhosis represents a worldwide health problem and is a major cause of mortality. Cirrhosis is the result of extensive hepatocyte death and fibrosis induced by chronic alcohol abuse and hepatitis B and C viruses. Successful gene therapy approaches to this disease may require both reversal of fibrosis and stimulation of hepatocyte growth. Urokinase-type plasminogen activator (uPA) may serve this function, as it is an initiator of the matrix proteolysis cascade and induces hepatocyte growth factor expression. In a rat cirrhosis model, a single iv administration of a replication-deficient adenoviral vector encoding a nonsecreted form of human uPA resulted in high production of functional uPA protein in the liver. This led to induction of collagenase expression and reversal of fibrosis with concomitant hepatocyte and improved liver function. Thus, uPA gene therapy may be an effective strategy for treating cirrhosis in humans.
Salgado
S
S
Institute Molecular Biology in Medicine and Gene Therapy, CUCS, Harvard Gene Therapy Initiative, Guadalajara, Jalisco, 44281, Mexico.
Garcia
J
J
Vera
J
J
Siller
F
F
Bueno
M
M
Miranda
A
A
Segura
A
A
Grijalva
G
G
Segura
J
J
Orozco
H
H
Hernandez-Pando
R
R
Fafutis
M
M
Aguilar
L K
LK
Aguilar-Cordova
E
E
Armendariz-Borunda
J
J
D000818:Animals; D001483:Base Sequence; D002251:Carbon Tetrachloride / Q000633:toxicity; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D015316:Genetic Therapy; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D008115:Liver Regeneration / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics*
D017931:DNA Primers; D002251:Carbon Tetrachloride; D014568:Urokinase-Type Plasminogen Activator