Cellular sources of fibrotic collagen

Every somatic cell within vertebrate species contains genetic information and therefore the potential to synthesize collagen. Normally, when there is a requirement for new connective tissue following injury, cells of mesodermal origin are activated to meet that demand and supply sufficient amounts of collagen to return structure and function to the damaged tissue or organ. Under these conditions, nonconnective tissue cells either do not synthesize collagen or may produce only minute quantities which are barely detectable by our most sensitive techniques. However, when these nonmesodermal cells are exposed to an abnormal or toxic environment, collagen expression may become greatly enhanced. For example, when hepatocytes are removed from their normal in vivo environment and placed in cell culture, they demonstrate a dramatic increase in their potential to produce collagen. Hepatocytes may also express this ability to produce significant quantities of collagen when they are exposed to toxins or injury in vivo. The list of cells shown to produce collagen or contain enzymes related to collagen biosynthesis has expanded in recent years and now includes such diverse and specialized cells as glomerular mesangial, adipocytes, aortic endothelial, smooth muscle, Schwann cells, and lymphocytes. Therefore, the loss of structure and function in a tissue or organ due to fibrosis may result from excessive deposition of collagen from nonmesodermal sources as well as from connective tissue cells.