ABSTRACT
Activin is a member of the transforming growth factor beta (TGF-beta) family, which plays a crucial role in skin morphogenesis and wound healing. To gain insight into the underlying mechanisms of action, we searched for activin-regulated genes in cultured keratinocytes. One of the identified target genes encodes Id1, a negative regulator of helix-loop-helix transcription factors. We show that Id1, Id2, and Id3 are strongly downregulated by activin in keratinocytes in vitro and in vivo. To determine the role of Id1 in keratinocyte biology, we generated stable HaCaT keratinocyte cell lines overexpressing this protein. Our results revealed that enhanced levels of Id1 do not affect proliferation of keratinocytes in monoculture under exponential culture conditions or in response to activin or TGF-beta1. However, in three-dimensional organotypic cultures, Id1-overexpressing HaCaT cells formed a hyperthickened and disorganized epithelium that was characterized by enhanced keratinocyte proliferation, abnormal differentiation, and an increased rate of apoptosis. These results identify an important function of Id1 in the regulation of epidermal homeostasis.
Subject(s)
Activins/physiology , Epidermis/physiology , Homeostasis , Inhibitor of Differentiation Protein 1/physiology , Animals , Blotting, Western , Cell Division , Cell Line , Cells, Cultured , Epidermal Cells , Mice , Mice, Inbred BALB C , Mice, Transgenic , Nucleic Acid Hybridization , Wound HealingABSTRACT
Lipid peroxidation has been induced by means of an atherogenic diet causing hypercholesterolaemia, hypertriglyceridaemia, increased LDL and decreased HDL serum fractions in addition to the fatty degeneration, vacuolization of the liver cells and accumulation of malondialdehyde in the liver. Increased release of acid phosphatase and N-beta-glucuronidase was also observed pointing to cholesterol-induced lysosomal membrane damage. In response to pretreatment with, and simultaneous administration of, 6,6'-methylene bis (2,2-dimethyl-4-methane sulphonic acid sodium salt-1,2-dihydroquinoline) the signs and symptoms of fatty liver degeneration, the tissue, plasma and platelet malondialdehyde concentrations and the LDL serum fraction significantly decreased and HDL serum fraction increased. Lisosomal membrane stability was restored, resulting in physiological acid phosphatase and N-beta-glucuronidase activities. The pathological and clinical aspects of lipid peroxidation in several diseases of the digestive organs and the suggested therapeutic uses of non-toxic radical scavengers have been outlined.