Abstract
Biography
Background: Tubulointerstitial fibrosis (TIF) is one of the main pathological features of various progressive renal damages and chronic kidney diseases. Mesenchymal stromal cells (MSCs) have been verified with significant improvement in the therapy of fibrosis diseases, but the mechanism is still unclear. We attempted to explore the new mechanism and therapeutic target of MSCs against renal fibrosis based on renal proteomics. Methods: TIF model was induced by adenine gavage. Bone marrow-derived MSCs were injected by the tail vein after modeling. Renal function and fibrosis-related parameters were assessed by Masson, Sirius red, immunohistochemistry, and western blot. Renal proteomics was analyzed using iTRAQ-based mass spectrometry. A further possible mechanism was explored by the transfected galectin-3 gene for knockdown (Gal-3 KD) and overexpression (Gal-3 OE) in HK-2 cells with a lentiviral vector. Results: MSCs treatment clearly decreased the expression of α-SMA, collagen type I, II, III, TGF-β1, Kim-1, p-Smad2/3, IL-6, IL-1β, and TNFα compared with model rats, while p38 MAPK increased. Proteomics showed that only 40 proteins exhibited significant differences (30 upregulated, 10 downregulated) compared the MSCs group with the model group. Galectin-3 was downregulated significantly in renal tissues and TGF-β1-induced rat tubular epithelial cells and interstitial fibroblasts, consistent with the iTRAQ results. Gal-3 KD notably inhibited the expression of p-Akt,
p-GSK3β, and snail in TGF-β1-induced HK-2 cells fibrosis. On the contrary, Gal-3 OE obviously increased the expression of p-Akt, p-GSK3β, and snail. Conclusion: The mechanism of MSCs' anti-renal fibrosis was probably mediated by galectin-3/Akt/GSK3β/Snail signaling pathway. Galectin-3 may be a valuable target for treating renal fibrosis.
Keywords: Adenine, Mesenchymal stem cells, Interstitial fibrosis, Galectin-3, Proteomics
Background: Tubulointerstitial fibrosis (TIF) is one of the main pathological features of various progressive renal damages and chronic kidney diseases. Mesenchymal stromal cells (MSCs) have been verified with significant improvement in the therapy of fibrosis diseases, but the mechanism is still unclear. We attempted to explore the new mechanism and therapeutic target of MSCs against renal fibrosis based on renal proteomics. Methods: TIF model was induced by adenine gavage. Bone marrow-derived MSCs were injected by the tail vein after modeling. Renal function and fibrosis-related parameters were assessed by Masson, Sirius red, immunohistochemistry, and western blot. Renal proteomics was analyzed using iTRAQ-based mass spectrometry. A further possible mechanism was explored by the transfected galectin-3 gene for knockdown (Gal-3 KD) and overexpression (Gal-3 OE) in HK-2 cells with a lentiviral vector. Results: MSCs treatment clearly decreased the expression of α-SMA, collagen type I, II, III, TGF-β1, Kim-1, p-Smad2/3, IL-6, IL-1β, and TNFα compared with model rats, while p38 MAPK increased. Proteomics showed that only 40 proteins exhibited significant differences (30 upregulated, 10 downregulated) compared the MSCs group with the model group. Galectin-3 was downregulated significantly in renal tissues and TGF-β1-induced rat tubular epithelial cells and interstitial fibroblasts, consistent with the iTRAQ results. Gal-3 KD notably inhibited the expression of p-Akt,
p-GSK3β, and snail in TGF-β1-induced HK-2 cells fibrosis. On the contrary, Gal-3 OE obviously increased the expression of p-Akt, p-GSK3β, and snail. Conclusion: The mechanism of MSCs' anti-renal fibrosis was probably mediated by galectin-3/Akt/GSK3β/Snail signaling pathway. Galectin-3 may be a valuable target for treating renal fibrosis.
Keywords: Adenine, Mesenchymal stem cells, Interstitial fibrosis, Galectin-3, Proteomics
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