1. Transcriptional activation of matrix genes by transforming growth factor beta 1 in mesangial cells
S Suzuki, I Ebihara, Y Tomino, H Koide Exp Nephrol. 1993 Jul-Aug;1(4):229-37.
The accumulation of mesangial matrix is a common histologic abnormality observed over the course of various glomerular diseases. To examine the role of transforming growth factor beta 1 (TGF-beta 1), a well-known regulator of extracellular matrix metabolism, in such processes, we studied the effects of this peptide on the gene expression of extracellular matrix components in cultured rat mesangial cells. TGF-beta 1 increased the mRNA levels for alpha 1 (I) and alpha 1 (IV) collagens and fibronectin. The increase in these mRNA levels was detectable 6 h after stimulation by TGF-beta 1. At 24 h, the mRNA levels for alpha 1 (I) and alpha 1 (IV) collagens and fibronectin increased 1.9-, 2.8- and 2.6-fold, respectively, above their basal levels. Concomitant treatment with cycloheximide did not prevent the stimulation by TGF-beta 1 and resulted in exceptional superinduction for the fibronectin gene. Concomitant treatment with actinomycin D completely inhibited the increase in the mRNA levels induced by TGF-beta 1. Furthermore, TGF-beta 1 showed no stabilizing effect on the transcripts. These results suggest that TGF-beta 1, which is released in glomerular injury, induces an increase in the transcription of the alpha 1 (I) and alpha 1 (IV) collagen and fibronectin genes in mesangial cells and may mediate the accumulation of the extracellular matrix in the mesangium.
2. Introduction of N-cadherin-binding motif to alginate hydrogels for controlled stem cell differentiation
Jae Won Lee, Hyoseok An, Kuen Yong Lee Colloids Surf B Biointerfaces. 2017 Jul 1;155:229-237. doi: 10.1016/j.colsurfb.2017.04.014. Epub 2017 Apr 9.
Control of stem cell fate and phenotype using biomimetic synthetic extracellular matrices (ECMs) is an important tissue engineering approach. Many studies have focused on improving cell-matrix interactions. However, proper control of cell-cell interactions using synthetic ECMs could be critical for tissue engineering, especially with undifferentiated stem cells. In this study, alginate hydrogels were modified with a peptide derived from the low-density lipoprotein receptor-related protein 5 (LRP5), which is known to bind to N-cadherin, as a cell-cell interaction motif. In vitro changes in the morphology and differentiation of mouse bone marrow stromal cells (D1 stem cells) cultured in LRP5-alginate hydrogels were investigated. LRP5-alginate gels successfully induced stem cell aggregation and enhanced chondrogenic differentiation of D1 stem cells, compared to RGD-alginate gels, at low cell density. This approach to tailoring synthetic biomimetic ECMs using cell-cell interaction motifs may be critical in tissue engineering approaches using stem cells.
3. Glomerular expression of matrix metalloproteinases in systemic lupus erythematosus in association with activity index and renal function
Konstantinos N Adamidis, et al. Ren Fail. 2019 Nov;41(1):229-237. doi: 10.1080/0886022X.2019.1591998.
Purpose: The aim of this study was to examine the expression of matrix metalloproteinases (MMPs) MMP-1, MMP-2, MMP-3, MMP-9, and their specific tissue inhibitor TIMP-1 in kidney biopsies of patients with lupus nephritis (LN) and to investigate the relationship between MMPs, activity index, and renal function at the time of kidney biopsy. Methods: We performed immunohistochemistry with monoclonal antibodies against MMP-1, MMP-2, MMP-3, MMP-9, and TIMP-1 in 58 kidney-biopsy specimens with LN (according to the 2004 ISN/RPS classification) and eight specimens from normal kidney tissue. We used clinical data of 36 patients at the time of kidney biopsy to evaluate the association between MMPs expression and renal function. Results: We found increased MMP-1, MMP-2, and MMP-3 expression in LN glomeruli and a significant correlation with the activity features, with higher activity index score and worse renal function (p < .001). In particular, we have noticed a significant correlation of MMP-1 with leukocyte influx (OR:16.5 95%CI 4.3-62.5 p < .001), and MMP-3 with glomerular hypercellularity (OR:18.6 95%CI 4.8-72.8 p < .001). Moreover, we found a strong correlation of MMP-2 expression with fibrinoid necrosis and cellular crescents formation (OR:17.1 95%CI 4.3-67.7 p < .001). Conclusions: MMP expression in renal biopsy of patients with LN is increased and directly related to a highly active inflammatory response. Moreover, stronger MMP expression is associated with higher activity index and a more profound renal dysfunction.
