scholarly journals Role of Nampt-Sirt6 Axis in Renal Proximal Tubules in Extracellular Matrix Deposition in Diabetic Nephropathy

Cell Reports ◽  
2019 ◽  
Vol 27 (1) ◽  
pp. 199-212.e5 ◽  
Author(s):  
Hirokazu Muraoka ◽  
Kazuhiro Hasegawa ◽  
Yusuke Sakamaki ◽  
Hitoshi Minakuchi ◽  
Takahisa Kawaguchi ◽  
...  
Author(s):  
Wen Shi ◽  
Yan Wu ◽  
Donghui Bian

Hypertrophic scar (HS) results from abnormal wound healing, accompanied by excessive hypercellularity, migration and extracellular matrix (ECM) deposition. Autophagy dysregulation plays crucial roles during HS formation. The overexpressed p75 neurotrophin receptor (p75NTR) in injured skin tissue after wound healing becomes a factor aggravating scar. The study was designed to investigate the role of p75NTR and p75NTR-mediated autophagy in the process of HS. The results revealed that p75NTR expression was significantly upregulated while that of autophagy proteins was downregulated in cicatrix at 3 and 6 months after burn, which was recovered at 12 months. p75NTR silencing inhibited proliferation, migration and ECM deposition of hypertrophic scar fibroblasts (HSF), whereas p75NTR overexpression presented the opposite results. Silencing of p75NTR reduced the expression of PI3K/Akt/mTOR signaling molecules while enhanced that of autophagy proteins. Importantly, PI3K agonist (IGF-1) intervention notably decreased the levels of LC3B II/I and Beclin-1, and restored the inhibitory effects of p75NTR silencing on proliferation, migration and ECM deposition of HSF. Concurrently, autophagy inhibitor 3-methyladenine (3-MA) treatment exhibited the same variation trends with IGF-1. Taken together, these findings demonstrated that p75NTR silencing inhibits proliferation, migration and ECM deposition of HSF by activating autophagy through inhibiting PI3K/Akt/mTOR pathway.


2009 ◽  
Vol 379 (2) ◽  
pp. 411-416 ◽  
Author(s):  
Seiya Sato ◽  
Harukiyo Kawamura ◽  
Minoru Takemoto ◽  
Yoshiro Maezawa ◽  
Masaki Fujimoto ◽  
...  

2019 ◽  
Vol 303 (6) ◽  
pp. 1703-1716 ◽  
Author(s):  
Obianamma E. Onochie ◽  
Anwuli J. Onyejose ◽  
Celeste B. Rich ◽  
Vickery Trinkaus‐Randall

F&S Science ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 78-89
Author(s):  
Justin Pilgrim ◽  
Jacquel Arismendi ◽  
Anthony DeAngelis ◽  
Terrence Lewis ◽  
Joy Britten ◽  
...  

2020 ◽  
Vol 19 (4) ◽  
pp. 739-744
Author(s):  
Xi Zhao ◽  
Yao-Guang Wang ◽  
Xi-kai Yang ◽  
Man Li ◽  
Shi-Jie Liu ◽  
...  

Purpose: To investigate the anti-fibrotic effects of tanshinone IIA (TS) on renal tubular epithelial cells (HK-2 cells) under high glucose conditions and their related molecular mechanism(s) of action.Methods: After treatment with TS (6 μg/mL) for 24 h, the morphology of HK-2 cells stimulated by high glucose was observed under the microscope. Additionally, potential mechanisms related to the antifibrosis effects of TS were evaluated using western blotting assay and quantitative real time PCR (qRTPCR), including transforming growth factor (TGF) β1, α-smooth muscle actin (α-SMA), heme oxygenase 1 (HO-1), laminin (LN), fibronectin (FN), and E-cadherin (E-cad).Results: A high-glucose culture environment induced fibrosis of HK-2 cells, as indicated by changes in cell morphology. The anti-fibrotic effects of TS were mainly associated with a decrease in the expression levels of TGF-β1, α-SMA and LN, while the expression of E-cad increased. These resultsalso revealed that TS increased the expressions of HO-1.Conclusion: The findings suggest that TS suppresses fibrosis caused by high glucose in HK-2 cells by inhibiting extracellular matrix deposition and epithelial-mesenchymal transition and by reducing oxidative stress. Further investigations are needed to evaluate the clinical application of this compound in diabetic nephropathy. Keywords: Tanshinone IIA, Diabetic nephropathy, HK-2 cells, Fibrosis


2021 ◽  
Author(s):  
Hao Li ◽  
Mengna Li ◽  
Pei Liu ◽  
Kai-Yang Wang ◽  
Haoyu Fang ◽  
...  

Due to the native skin limitations and the complexity of reconstructive microsurgery, advanced biomaterials are urgently required to promote wound healing for severe skin defects caused by accidents and disasters....


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