The Molecular Mechanism Of Heat Shock Protein 47 In The Development Of Pathological Scars

BackgroundsIt has become a focus project to study the mechanism of pathological scars formation for the kingdom of plastic surgery or even all surgery. Being the complexity of the mechanism, there is none of etiological judgments and effective therapeutic methods to it so far. It has been shown in many investigations, that the abnormally increasing production and deposition of collagen is one of the important mechanisms of pathological scars and other fibrotic diseases.Heat shock protein (HSP) 47 is a resident Endoplasmic Reticulum protein , first identified as the major collagen-binding heat-inducible glycoprotein in fibroblasts. It is characterized not only by its substrate specificity for collagen but also by its correlational expression with that of various types of collagens in various tissues and under some pathophysiological conditions like fibrosis. Hsp47 is an essential protein for the synthesis and processing of various types of collagen. It has been shownin many investigations, antisense oligonucleotides against Hsp47 suppress collagen accumulation in experimental glomeruloneophritis. These also demonstrated that antisense treatment against Hsp47 reduced the formation of scars substantially following the wounding the of rats' backs in vivo.With rapid development of the techniques of genetic engineering, gene therapy has become a kind of brand-new therapeutic method. It will become the hot problem in plastic surgery to cure pathological scars by gene therapeutic method.MethodsThe main techniques we adopted include RNA inferencing, real time RT-PCR, plasmid building, immunohistochemistric staining, sinus red staining and polarization microscopy observing, hydroxyproline assay, western blotting, et al. Based on comparison of difference of HSP47 expression between pathological scars and normal skins, we designed and built Hsp47 siRNA plasmids. After specifically down-regulating the expression of Hsp47 gene in keloid fibroblasts, we detected the collagen fiber contents and analyzed the significance of the results.ResultsCompared with normal skin tissues, the protein and mRNA expression of Hsp47 were significantly higher in pathological scars tissues (PO.01) . And there was a positive correlation between the expression of Hsp47 and the total collagen fiber contents ( r = 0.386, P<0.05 ) . After specifically down-regulating the expression of Hsp47 gene in keloid fibroblasts, theexpression of collagen mRNA and protein obviously reduced in cytoplasm and exocytic area.ConclusionsDuring the formation of pathological scars , there was the over-expression of Hsp47 gene in fibroblasts. After its transcription and translation, a great quantity of Hsp47 proteins deposited in Endoplasmic Reticulum, which lead to the increase of synthesis and secretion of collagen. In this way, excessive collagen deposited in dermis, which caused the formation of pathological scars.The mechanism, that Hsp47 promoting the keloid formation, provided a new target to treat keloid and a theoretical base to cure pathological scars by gene therapeutic method.