The Imbalance of MMP-2/TIMP-2 and MMP-9/TIMP-1 Contributes to Collagen Deposition Disorder in Diabetic Non-Injured Skin

Abstract

The importance of the early diagnosis and treatment of diabetes and its cutaneous complications has become increasingly recognized. When diabetic non-injured skin was stained with Masson's trichrome, its dermal collagen was found to be disordered, its density was variable, and it was dispersed or arranged in vague fascicles. The collagen type I sequencing results of RNA sequencing-based transcriptome analysis of three primary human skin cell types-dermal fibroblasts, dermal microvascular endothelial cells, and epidermal keratinocytes-under high glucose were analyzed. The results showed that both COL1A1 and COL1A2 mRNA expressions were reduced in human dermal fibroblasts (HDFs). The ratio of matrix metalloproteinase (MMP)-2/tissue inhibitors of metalloproteinase (TIMP)-2 and MMP-9/TIMP-1 in HDFs increased when treated with high glucose. By inhibiting MMP-2 and MMP-9 with SB-3CT, collagen deposition disorder of the skin in streptozotocin-induced diabetes mice was alleviated. The imbalance of MMP2/TIMP2 and MMP9/TIMP1 contributes to the non-injured skin disorder of collagen deposition in diabetes, suggesting a possibility for early treatment of diabetes skin complications.

Keywords: MMPs (metalloproteinases); TIMPs; collagen; diabetes; skin.