TIMP3

Case Study 1: Viviana Casagrande, 2021

Diabetic nephropathy (DN), one of the major complications of diabetes, is characterized by albuminuria, glomerulosclerosis, and progressive loss of renal function. Loss of TIMP3, an Extracellular Matrix bound protein affecting both inflammation and fibrosis, is a hallmark of DN in human subjects and mouse models. This study was designed to provide evidences that the modulation of the system involving TIMP3 and its target A Disintegrin And Metalloproteinase 17 (ADAM17), may rescue kidney pathology in diabetic mice. DBA/2J mice were administered new peptides based on the human TIMP3 N-terminal domain, specifically conjugated with G3C12, a carrier peptide highly selective and efficient for transport to the kidney. Twelve weeks after Streptozotocin injections, 24-hour albuminuria was determined by ELISA, kidney morphometry was analyzed by periodic acid-shift staining, and Real Time-PCR and western blot analysis were performed on mRNA and protein extracted from kidney cortex. The results showed that both genetic modifications and peptides treatment positively affect renal function and structure in diabetic mice, as indicated by a significant and consistent decline in albuminuria along with reduction in glomerular lesions, as indicated by reduced mesangial expansion and glomerular hypertrophy, decreased deposition of extracellular matrix in the mesangium, diminished protein expression of the NADPH oxidases 4 (NOX4).

Fig1. Inhibition of human MMP2, MMP9, and ADAM17 enzyme activity.

Fig2. Protein expression in kidney cortex.

Case Study 2: Sunyoung Park, 2019

The human skin is the outermost physical barrier and has its own circadian machinery that works either cooperatively with the central clock, or autonomously. Circadian rhythms have been observed in many functions related to epidermal homeostasis including hydration and inflammation, and this functional oscillation is disturbed by ultraviolet radiation (UVR), which is a strong environmental cue. Among the genes estimated to show circadian expression in the skin, metalloproteinase inhibitor 3 (TIMP3), has a rhythmic expression in synchronized human keratinocytes similar to that of the core clock gene PER1 and an epidermal circadian regulatory gene, aquaporin 3 (AQP3) but was antiphase to the core clock gene BMAL1. Tumor necrosis factor-α (TNF-α), the regulatory target of TIMP3 via a disintegrin and metalloproteinase domain 17 (ADAM17), was inversely regulated when TIMP3 expression was downregulated by ultraviolet B (UVB) treatment. When synthetic TIMP3 peptides were applied to the cells, the secretion of TNF-α did not increase following the UVB treatment. Similar to TIMP3 peptides, Camellia sinensis leaf-derived extracts showed a distinguishing efficacy in recovering TIMP3 expression, downregulated by UVB treatment.

Fig3. The secreted or cytosolic TIMP3 and aquaporin 3 (AQP3) were examined at ZT 8 and 24 after UVB irradiation.

Fig4. NHEKs were irradiated following each scheme and harvested every 4 h.

Fig1. A schematic diagram of the proposed mechanism of cisplatin sensitivity enhancement by TIMP3 overexpression. (Xiu-Guo Han, 2018)

Fig2. Proposed model of TIMP3 regulation of cerebral arterial tone and CBF responses. (Carmen Capone, 2016)

TIMP3 involved in several pathways and played different roles in them. We selected most pathways TIMP3 participated on our site, such as Proteoglycans in cancer, MicroRNAs in cancer, which may be useful for your reference. Also, other proteins which involved in the same pathway with TIMP3 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

TIMP3 has several biochemical functions, for example, metal ion binding, metalloendopeptidase inhibitor activity, protease binding. Some of the functions are cooperated with other proteins, some of the functions could acted by TIMP3 itself. We selected most functions TIMP3 had, and list some proteins which have the same functions with TIMP3. You can find most of the proteins on our site.

TIMP3 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with TIMP3 here. Most of them are supplied by our site. Hope this information will be useful for your research of TIMP3.

AGTR2; ADAMTS5

Research Area

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