Search

Background: Activin-A may exert pro- or anti-tumorigenic activities depending on cellular context. However, little is known about its role, or the other mature activin proteins, in colorectal carcinoma (CRC). This study measured the expression of activin βA- & βB-subunits, activin type IIA & IIB receptors, smads 2/3/4/6/7 and follistatin in CRC induced by azoxymethane (AOM) in rats. The results were compared with controls and disseminated according to the characteristics of histopathological lesions., Methods: Eighty male Wistar rats were allocated into 20 controls and the remaining were equally divided between short 'S-AOM' (15 weeks) and long 'L-AOM' (35 weeks) groups following injecting AOM for 2 weeks. Subsequent to gross and histopathological examinations and digital image analysis, the expression of all molecules was measured by immunohistochemistry and quantitative RT-PCR. Activin-A, activin-B, activin-AB and follistatin were measured by ELISA in serum and colon tissue homogenates., Results: Colonic pre-neoplastic and cancerous lesions were identified in both AOM groups and their numbers and sizes were significantly (P < 0.05) greater in the L-AOM group. All the molecules were expressed in normal colonic epithelial cells. There was a significantly (P < 0.05) greater expression of βA-subunit, IIB receptor and follistatin in both pre-neoplastic and cancerous tissues. Oppositely, a significant (P < 0.05) decrease in the remaining molecules was detected in both AOM groups. Metastatic lesions were only observed within the L-AOM group and were associated with the most significant alterations of all molecules. Significantly higher concentrations of activin-A and follistatin and lower activin-AB were also detected in both groups of AOM. Tissue and serum concentrations of activin-A and follistatin correlated positively, while tissue activin-AB inversely, and significantly with the numbers and sizes of colonic lesions., Conclusions: Normal rat colon epithelial cells are capable of synthesising, controlling as well as responding to activins in a paracrine/autocrine manner. Colonic activin systems are pathologically altered during tumorigenesis and appear to be time and lesion-dependent. Activins could also be potential sensitive markers and/or molecular targets for the diagnosis and/or treatment of CRC. Further studies are required to illustrate the clinical value of activins and their related proteins in colon cancer.

The importance of activins and follistatin in liver diseases has recently emerged. The aim of the present study was to measure the influence of chronic infection with viral hepatitis C (CHC) genotype 1 and 4 on serum levels of activin-A, activin-B and follistatin, and to determine their correlations with viral load, liver damage, interleukin-6 (IL-6) and tumour necrosis factor (TNF)-α. Sera samples collected from 20 male and 20 female treatment naïve CHC genotype 1 and 4 Saudi patients (ten males and ten females for each genotype), and 40 gender- and age-matched healthy participants were analysed for activin-A, activin-B and follistatin using enzyme-linked immunosorbent assay and their levels were correlated with IL-6, TNF-α, viral load and AST platelet ratio index (APRI). Serum activin-A, activin-B, IL-6 and TNF-α were significantly increased, while serum follistatin was significantly decreased, in both genders of CHC patients compared with control subjects, In both viral genotypes, activin-A was strongly and positively correlated with the viral load, APRI, IL-6 and TNF-α, and negatively with albumin (P < 0.01). Activin-B showed the same correlations of activin-A only in CHC genotype 1 patients, but it was weaker than activin-A. No correlation was detected with follistatin. Serum activins, particularly activin-A, and follistatin are significantly altered by CHC genotype 1 and 4. This dysregulation of activins/follistatin axis may be associated with viral replication, host immune response and liver injury. Further studies are needed to illustrate the definite role(s) and clinical value of activins and follistatin in CHC.

Aims: To measure the expression of activin βA-subunit, activin IIA and IIB receptors, Smad4, Smad7, and follistatin in the liver and the liver and serum concentrations of mature activin-A and follistatin in normal rat following treatment with pegylated interferon-α (Peg-INF-α) and ribavirin (RBV)., Materials and Methods: 40 male Wistar rats were divided equally into 4 groups: "control," "Peg-only" receiving 4 injections of Peg-INF-α (6 µg/rat/week), "RBV-only" receiving ribavirin (4 mg/rat/day) orally, and "Peg & RBV" group receiving both drugs. The expression of candidate molecules in liver was measured by immunohistochemistry and quantitative PCR. The concentrations of mature proteins in serum and liver homogenate samples were measured using ELISA., Results: Peg-INF-α  ± RBV altered the expression of all candidate molecules in the liver at the gene and protein levels (P < 0.05) and decreased activin-A and increased follistatin in serum and liver homogenates compared with the other groups (P < 0.05). There were also significant correlations between serum and liver activin-A and follistatin., Conclusion: Peg-INF-α modulates the hepatic production of activin-A and follistatin, which can be detected in serum. Further studies are needed to explore the role of Peg-INF-α on the production of activins and follistatin by the liver and immune cells.