Imbalance of MMP-9/TIMP-1 during the cutaneous "underlying disorder" in diabetic rats / 中华内分泌代谢杂志

ABSTRACT

Objective To investigate the change of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the skin of diabetic rats, and to explore the potential role of MMP-9/TIMP-1. Methods Diabetic rats were induced with streptozotocin (STZ). Then all rats were maintained for 6 weeks. Routine pathological examination and immnnohistochemistry were made to reveal the histological and cytological appearances. RT-PCR and Western blotting were used to detect the expression of mRNA and protein of MMP-9 and TIMP-1 in the skin. Results Six weeks after STZ treatment, examination of HE-stained skin sections from normal and diabetic animals revealed that the epidermis and dermis layers were thinner in diabetic rats than those in control rats. The skin of diabetic rats showed features of atrophy such as disorganization of connective tissue fiber bundles and enlarged space between collagen fiber bundles. In contrast, thick bundles of connective tissue were observed in the dermis of normal rat skin. In normal skin, cells had a bipolar, spindle-shaped appearance in the thick collagen bundles, while in the skin of diabetic animals the interstitial cells had a rounded, shrunken and crenated appearance. The relative values of expression of MMP-9 in diabetic group were higher than those in normal group with significant difference, however, the relative values of expression of TIMP-I in diabetic group were lower than those in control group. Conclusion The changes in cutaneous histology and cytology appear earlier than skin wound. These "underlying disorders" may be associated with the imbalance of MMP-9/TIMP-1.