Chronic Cellular Injury and Human Proliferative Disorders
Carcinogenesis and normal tissue regeneration share some common characteristics. In both states there is an active cellular proliferation and induction of the expression of potent mitogenic growth factors and receptors that promote the proliferative activity. Normal tissue regeneration is initiated by acute injury. Carcinogenesis is linked to prolonged chronic cellular injury by a variety of toxic agents including carcinogen. The major difference between the two processes is that in normal tissue repair, both cellular proliferation and growth factor expression are suppressed upon the healing of the wound. In contrast, in cancer and in some nonmalignant proliferative disorders cellular proliferation remains uncontrolled, and the expression of the mitogenic growth factors and receptors remains unsuppressed. It seems that in these disorders, the pathologic lesion is not the induction of growth factor and cytokine expression. Induction of these factors in response to acute or chronic injury appears to be a physiologic process aiming at the repair of the damage caused by the injury. What is abnormal in these pathologic states is a malfunction of the reversal mechanisms that normally control the suppression of the genes encoding for these growth factors and cytokines.
KeywordsIdiopathic Pulmonary Fibrosis Chronic Injury Acute Injury Growth Factor Expression Transform Growth Factor Alpha
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