Bone marrow mesenchymal stromal cells with CD47 high expression via the signal transducer and activators of transcription signaling pathway preventing myocardial fibrosis.

UNLABELLED: This study was initiated to investigate the efficacy of myocardial fibrosis intervention via signal transducer and activators of transcription (STAT) signaling using bone marrow (BM) mesenchymal stromal cells (MSC) in which being over-expressed with the aid of bispecific antibody (BiAb) and ultrasound-mediated microbubbles (MB). BiAb was prepared and combined with isolated MSC with CD47 overexpression from male mice and trans-fused into female mice with isoproterenol-induced myocardial fibrosis via the tail vein, followed by MB. This study included five groups. Five weeks after treatment, expression levels of the sex-determining region of Y-chromosome (SRY), matrix metalloproteinases (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1 and vascular endothelial growth factor (VEGF) in myocardium were detected by fluorescent quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of signal transducer and activators of transcription (STAT) 1 and STAT 3 was detected by Western blot. RESULTS: The highest homing number of MSC was in the CD47 + MSC + BiAb + MB group, second highest in the CD47 + MSC + BiAb group, and lowest in MSC alone. Compared with the Control group, CD47 + MSC + BiAb + MB, CD47 + MSC + BiAb, CD47 + MSC and MSC groups had decreased levels of MMP-9, TIMP-1, STAT 1 and collagen deposition, and increased levels of STAT 3. Up regulated STAT 3 and down regulated TIMP-1 were significantly different in CD47 + MSC + BiAb + MB compared with CD47 + MSC or CD47 + MSC + BiAb. CONCLUSION: CD47 can enhance the homing rate and repairing efficacy of MSC. MSC can improve MMP-TIMP expression in injured myocardium and interfere with myocardial fibrosis after homing, a mechanism that may be related to the STAT-mediated signaling pathway.

[Intestinal Absorption Characteristics and Mechanism of Polygala tenuifolia Hydrolysate in Rats].

OBJECTIVE: To evaluate the absorption feature and mechanism of tenuifolin(TF) and polygalaxanthone III (PT) in different intestinal parts of rats and the impact of MRP2 and P-glycoprotein (P-gp) on it. METHODS: In situ unidirectional perfusion was used to detect the concentration of TF and PT through HPLC-DAD with gravimetric method. Furthermore, impact of different parts, cosolvents and inhibitors to TF and PT was also explored with data of Ka and Papp. RESULTS: Tween as cosolvent, Ka and Papp of TF was significantly higher in colon than in other intestinal parts(P <0. 05 or P <0. 01). Whereas, Ka of PT was in sequence of colon, duodenum, jejunum, ileum,but with no significant difference among them(P >0. 05). SDS as cosolvent, Papp of TF was higher in colon than in duodenum(P <0. 05). K. of TF was significantly higher compared with control when added with VH, an inhibitor of P-gp(P <0. 05). In addition, Papp of PT in different concentration of VH increased(P <0. 05, P <0. 01). Papp of TF significantly increased with IT at the concentration of 0. 02 and 0. 04 mmol/L, an inhibitor of MRP2(P <0. 05, P <0. 01). Meanwhile, Ka of PT,with IT at the concentration of 0. 04 and 0. 08 mmol/L, was significantly higher(P <0. 05, P <0. 01). CONCLUSION: TF is mainly absorbed in colon, whereas PT is in duodenum. P-gp but not MRP2 influences the intestinal absorption of TF, indicating TF as substrate of P-gp. However, both of P-gp and MRP2 impact the absorption of PT, illustrating PT as substrate of P-gp and MRP2. It also indicates that inhibitors of P-gp and/or MRP2 in combined application may improve the absorption of PT and TF.