Role of transforming growth factor beta 1 on hepatic regeneration and apoptosis in liver diseases.

Abstract

Aims-To investigate the effects of transforming growth factor P1 (TGF-,1) on regeneration and induction of apoptosis of liver cell and bile duct in various liver diseases. Methods-Formalin fixed paraffin wax sections of 18 liver tissue samples were obtained by needle biopsy, surgery, or necropsy; these included six liver cirrhosis, three obstructive jaundice; five fulminant hepatitis, one subacute hepatitis, and three normal liver. Expression of TGF-p1, apoptosis related Ley antigen, Fas antigen, a receptor for tumour necrosis factor, and biotin nick end labelling with terminal deoxynucleotidyl transferase mediated dUTP (TUNEL) for locating DNA fragmentation, was investigated histochemically.

Critical Role of Smads and AP-1 Complex in Transforming Growth Factor-β-dependent Apoptosis

“…Smad3 knockout mice develop metastatic colorectal cancer (41). On the other hand, TGF-␤1 has been implicated as inducing apoptosis to eliminate abnormal cells from normal tissues such as the liver and prostate (4)(5)(6). Loss of sensitivity to the apoptotic effect of TGF-␤1 could contribute to the development of hepatocellular carcinoma and prostatic tumor.…”

“…Its apoptotic activity is also shown in specific cell types such as hepatocytes, myeloid cells, and epithelial cells. TGF-␤1 promotes apoptosis not only in a hepatoma cell line (3) but also in hepatocytes in regressing liver (4) and in cirrhotic liver (5). TGF-␤1 is implicated in the induction of apoptosis in prostatic epithelial cells after castration and is used to treat advanced prostatic tumor (6).…”

Molecular and Cell Biology of TGF-β

“…TGF-ß also plays a key role in regulating immune cell function, as illustrated both in escape from immune surveillance by cancer cells secreting excessive levels of TGF-ß, and in autoimmune disease where it both mediates tolerance and suppresses immune responses to local autoreactivity [63]. Recently, it has become appreciated that TGF-ß induces apoptosis of certain cells and that this mechanism may mediate, in part, its regulation of the balance of lineages of bone marrowderived cells [66], its control of hepatic regeneration [67], and its effects on tissue regression following hormone ablation in hormone-dependent tissues such as in mammary gland and prostate [68].…”

FoxO3a mediates transforming growth factor-β1-induced apoptosis in FaO rat hepatoma cells

“…Transforming growth factor-β1 (TGF-β1) is an important cytokine of cell homeostasis in the liver that inhibits cell proliferation and induces cell death (4)(5)(6). TGF-β primarily shows its apoptotic effect via release of cytochrome c and by activating the apoptotic protease-activating factor 1 (Apaf-1) apoptosome complex, which stimulates the caspase cascade (7).…”