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.

Sodium–glucose cotransporter-2 inhibitor alleviated atrial remodeling in STZ-induced diabetic rats by targeting TLR4 pathway

“…Evidences suggest that inflammation ( 14 ), oxidative stress ( 15 ), and mitochondrial dysfunction ( 16 ) were attributed to the fibrosis. The deposition of cardiac collagen fibers depends on the dynamic regulation process between metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cardiac tissue ( 17 ). However, in diabetes, the balance between MMP and TIMP is broken, resulting in excessive accumulation of collagen fibers ( 17 ).…”

“…The deposition of cardiac collagen fibers depends on the dynamic regulation process between metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cardiac tissue ( 17 ). However, in diabetes, the balance between MMP and TIMP is broken, resulting in excessive accumulation of collagen fibers ( 17 ). Suffering from ischemia, inflammation, and toxic insult, the normal myocardium was replaced with fibrous tissue, leading to structural remodeling ( 13 ).…”

MMP2 and MMP9 contribute to lung ischemia–reperfusion injury via promoting pyroptosis in mice

“…The experimental procedures were performed as our published paper described [ 34 ]. The extracted proteins were separated using 10% SDS electrophoresis before transfer onto a nitrocellulose membrane.…”

Role of matrix metalloproteinases in diabetic foot ulcers: Potential therapeutic targets

“…Endothelial cells that have been treated with exogenous MMP-2 have undergone dose-dependent morphologic alterations that are compatible with an angiogenic response ( Dean et al, 2007 ; Dean et al, 2007 ). However, an overactive MMP-2 protein causes an abnormal breakdown of the matrix and limits the production and remodeling of the new matrix, which can lead to a chronic wound ( Zhou et al, 2021 ). MMP-2 cleaves laminin-332 to stimulate the migration of keratinocytes, and it also releases an epidermal growth factor (EGF)-like fragment of the γ2-subunit short arm.…”