High glucose-induced Matrilin-2 expression in mouse mesangial cells was mediated by transforming growth factor beta 1 (TGF-β1)

Results of untargeted analysis using the SOMAscan proteomics platform indicates novel associations of circulating proteins with risk of progression to kidney failure in diabetes

“…Independent from the bioinformatics analysis, a manual literature review of the candidate proteins identified 6 proteins (DLL1, MATN2, ROR1, LAYN, MAPK11, and endostatin) implicated in kidney fibrosis in in vivo or in vitro studies. [16][17][18][19][20][21][22][23][24][25] Importantly, the first 3 proteins were also members of multiple neuron-related pathways, whereas the last 3 profibrotic proteins were not, suggesting their association with different mechanism of progressive kidney function decline. The role of the 2 other candidate proteins, ESAM and FABP3, could neither be classified as neuron-related pathway proteins nor as profibrotic proteins.…”

“…The results of the GO analysis and the manual literature review are shown in Table 3. [16][17][18][19][20][21][22][23][24][25] Importantly, 6 of 11 candidate proteins, LAYN, DLL1, MAPK11, MATN2, endostatin, and ROR1, were associated with kidney fibrosis in the manual review. 16,[19][20][21][22]24,25 Another 2 of 11 proteins, ESAM and NRX1B, were associated with adhesion of cells in the glomerulus.…”

“…[16][17][18][19][20][21][22][23][24][25] Importantly, 6 of 11 candidate proteins, LAYN, DLL1, MAPK11, MATN2, endostatin, and ROR1, were associated with kidney fibrosis in the manual review. 16,[19][20][21][22]24,25 Another 2 of 11 proteins, ESAM and NRX1B, were associated with adhesion of cells in the glomerulus. 17,18,23 The remaining 3 proteins, FABP3, KLK8, and RTN4R, were not previously reported to be associated with kidney diseases.…”

EP4 knockdown alleviates glomerulosclerosis through Smad and MAPK pathways in mesangial cells

“…EP4 flox/flox cells were also divided into four groups: 1, EP4 flox/flox + AD-GFP group; 2) EP4 flox/flox + AD-GFP + TGF-β1 group; 3, EP4 flox/flox + AD-CRE group; 4, EP4 flox/flox + AD-CRE + TGF-β1 group. Prior to the experiments, the cells were incubated in serum-free medium for 24 h. The optimum dose and reaction time of TGF-β1 (10 ng/ml, 24 h) was based on a previous study (14). Each individual assay was repeated at least three times with different cell preparations.…”

“…Certain chemical cytokines, including transforming growth factor (TGF)-β1, cause MCs to undergo a phenotype transformation to resemble fibroblasts, accompanied by the infiltration of inflammatory cells, causing glomerular scarring. This type of scarring eventually results in glomerular sclerosis (14). In patients with glomerulotubular imbalance, when glomerular filtration rate (GFR) declines to 10% of normal values, renal replacement therapy is required, as currently there is no specific treatment to reverse the progression.…”