DsbA-L mediated renal tubulointerstitial fibrosis in UUO mice

Abstract

Recent studies have reported that upregulation of disulfide-bond A oxidoreductase-like protein (DsbA-L) prevented lipid-induced renal injury in diabetic nephropathy (DN). However, the role and regulation of proximal tubular DsbA-L for renal tubulointerstitial fibrosis (TIF) remains unclear. In current study, we found that a proximal tubules-specific DsbA-L knockout mouse (PT-DsbA-L-KO) attenuated UUO-induced TIF, renal cell apoptosis and inflammation. Mechanistically, the DsbA-L interacted with Hsp90 in mitochondria of BUMPT cells which activated the signaling of Smad3 and p53 to produce connective tissue growth factor (CTGF) and then resulted in accumulation of ECM of BUMPT cells and mouse kidney fibroblasts. In addition, the progression of TIF caused by UUO, ischemic/reperfusion (I/R), aristolochic acid, and repeated acute low-dose cisplatin was also alleviated in PT-DsbA-L-KO mice via the activation of Hsp90 /Smad3 and p53/CTGF axis. Finally, the above molecular changes were verified in the kidney biopsies from patients with obstructive nephropathy (Ob). Together, these results suggest that DsbA-L in proximal tubular cells promotes TIF via activation of the Hsp90 /Smad3 and p53/CTGF axis.

Radical 1,4‐Aryl Migration Enabled Remote Cross‐Electrophile Coupling of α‐Amino‐β‐Bromo Acid Esters with Aryl Bromides

“…However, the formation of 5 was observed through 1 H NMR analysis via a radical cyclopropane ring‐opening reaction [Eq. (6)], which clearly indicates that the alkyl radical formed via dehalogenation by Ni likely triggered the sequential migration/cross‐coupling reaction [25] …”

“…indicates that the alkyl radical formed via dehalogenation by Ni likely triggered the sequential migration/cross-coupling reaction. [25] Based on the aforementioned experimental results and previously reported mechanisms, [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] ap ossible mechanism for the cascade reaction was proposed, as shown in Scheme 2. Ni II X 2 (dme) is reduced to aN i I -Ln species via as ingleelectron reduction process with Zn powder in the presence of the N ligand, which is then oxidatively treated with amino acid ester bromide (1a)t oy ield the alkyl radical (Int-I)a nd aN i II -Ln complex via as ingle-electron transfer process.A C!Ca tom aryl migration with concomitant C(sp 2 )-C(sp 3 ) bond homolytic cleavage (with abond dissociation energy of 72.9 kcal mol À1 )v ia as piro radical s-complex (Int-II)t hen occurs, [11] generating an a-aminoalkyl radical (Int-III), which is stabilised by the p-p conjugation effect with its adjacent electron-rich N atom.…”

Microinjection molding of polyoxymethylene/multiwalled carbon nanotubes composites with different matrix viscosities

“…There is growing interest in manufacturing polymeric microparts due to a trend of part miniaturization in the fields of electronics, automotive, biomedical and microelectromechanical systems (MEMS) among others. Some of the major polymers used in manufacturing polymeric microparts include poly(methyl methacrylate), polyethylene, polyoxymethylene (POM), poly(lactic acid) (PLA), liquid crystal polymers, polypropylene, and so forth 1–4 . Accordingly, several microprocessing technologies, such as microinjection molding (μIM), hot embossing, thermoforming, injection‐compression molding, and ultrasonic molding, 5,6 have been developed to satisfy ever‐increasing demands of miniature products from the above industrial sectors.…”

NCTD Prevents Renal Interstitial Fibrosis via Targeting Sp1/lncRNA Gm26669 Axis

“…These cells were cultured in an incubator at 37°C and with an atmosphere containing 5% CO 2 . The cellular model of fibrosis was created by adding 5 ng/ml of TGF-β1 to BUMPT cells and incubating for 24 h 21 , 22 . The intervention concentration of NCTD was 5 µg/ml.…”