Fibronectin is a glycoprotein of high molecular weight that can bind quite a number of intracellular and cellular components including collagen, actin, DNA as well as glycosaninoglycans. It is normally important in a number of fundamental cell processes including, cell- cell adhesion, cell migration and cell- to – extracellular matrix adhesion. The fibronectin is also found in the plasma, where it is involved in opnization and blood clot formation. Such a functional diversity of the fibronectin gene come due to alternative splicing of pre-mRNA, which lead to multiple protein isoforms which have unique biological properties.
(Peters, 1996) The fibronectin normally plays a crucial role in signal transaction as were as cell adhesion and is particularly regulated by TGF – B, a cytokine which plays a major role controlling the growth of transport hepatocytes. In its interactions with integrins, fibronectin can also directly influence gene transcription and cellular morphology in hepatocytes. It is normally hypothesized that abnormalities of fibronectin expression may play a crucial role in hepatocellular carcinoma (HCC) tumor biology.
Most of the previous studies have constantly demonstrated increased transcription of fibronection but protein expression results have been inconsistent. Hence, it is examined in its expression in HCC by immunohistochemistry. The subject provides the advantage of precise cellular localization, which is useful because cellular forms of fibronectin can be synthesized by a number of nonhepatocyte cell types, which reside in the liver, including stellate cells, macrophages as well as endothelial cells. (Peters, 1996) Aims and objectives Major projects (a) To study fibronectin protein
Specific objectives (i) To study functions of fibronectin protein in the livers of rats (ii) To study fibronectin protein and its overexperession. Background and significance Fibronectin plays a crucial role in cell migration, cell signaling, cell-to-cell adhesion as well as cell –to- extra cellular matrix adhesion. In the liver its expression has been studied basically as a component of the extra cellular matrix but little information is available on the expression of fibronectin protein in the neoplasic cells of hepatocellular carcinomas (HCCs).
When studied fifty-four surgically resected HCCS were immunostained with fibronectin. Tumor as well as normal liver tissues was analyzed concurrently in all cases, and expression in the tumor was then evaluated in comparison to the nonneoplastic liver. The case involved 54 adult rats out of them 30 were male and 24 were female. Fifty-one of the cases were classic HCCS including 24 cases moderately differentiated and 12 cases poorly differentiated. The remaining 12 cases were moderately differentiated fibrolameller carcinomas.
This shows in the normal liver, fibronectin labeled the sinusoids and weakly to moderately stained the cytoplasm of hepatocytes. In HCCS 30/54 showed over expression of fibronectin in the cytoplasm, 20/54 showed no change form nonneoplastic liver and one case showed decreased cytoplasmic staining. In addition, an abnormal membranous staining pattern was noted in 40/54 HCCS. In contrast to the HCCS, none of the 12-fibrolamellar carcinomas showed increased cytoplasmic staining. Excluding fibrolamellar carcinoma, increased cytoplasmic staining as well as, or membrane staining was not in the 49/51 (90%) of HCCs.
Then fibronection shown abnormal cytoplasm as well as, or membranous staining in the majority of HCCs. These implications of fibrionectin over expression are uncertain, however may reflect a turning point in tumor genesis. (Gregory, 1998) Fibronectin is useful and important in vitreoretinal pathology. Proliferative vitreonetinopathy (PUR) is such that it is characterized by cellular proliferation as well as the formation of intravitreal and periretinal membranes, which predispose traction retinal detachment.
In recent times fibronectin, the high molecular glycoprotein has been said to be important in the role of pathogenesis of PUR. In order to evaluate the importance of fibronectinn as a diagnostic are prognostic marker for PUR, it was determined that levels of immune reactive fibronectin may be in 59 rats vitreous specimens by a noncompetitive ELISA technique. Before the results of this study, fibronectin levels in the vitreous had not been properly investigated taking both protein as well as iron levels into consideration.
The vitreous was obtained during vitrectomies performed for a board range of vitreoretinal disorders. The measurements suggest that the amount of intravitreal fibronectin may be correlated with the seriousness of a manifested disorder rather than being diagnostic for PUR. (Paracer, 2000) Another area of significance is in the study of rheumatoid arthritis. Connective tissue cells into their environment and into the blood secrete Fibronectin as a glycoprotein. Normally plasma fibronectin has been isolated as well as used to prepare an antiserum.
This antiserum has been used in examining the distribution of this protein in the distribution of rheumatoid arthritis and in osteoarthritis, and in estimation of levels in plasma and synovial fluid. The results suggest that synovial cells synthesize fibronectin and the synovial fluid level of fibronectin was found to be about twice the plasma level in rheumatoid arthritis. Then the possible significant of local fibronectin production within joints in resolution r continuation of arthritis is discussed. (Markos, 2002)