Jingying Hou1, Lingyun Wang1, Jinghui Hou1, Tianzhu Guo1, Yue Xing1, Shaoxin Zheng1,2, Changqing Zhou1, Hui Huang1,2, Huibao Long1, Tingting Zhong1, Quanhua Wu1, Jingfeng Wang1,3, Tong Wang4,5,6. 1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China, 510120. 2. Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China. 3. Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China. 4. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, The Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China, 510120. tongwang316@163.com. 5. Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China. tongwang316@163.com. 6. Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, 107 Yanjiang Xi Road, Guangzhou, Guangdong, China. tongwang316@163.com.
Abstract
BACKGROUND: In this study, we hypothesized that activation of PPAR-γ enhanced MSCs survival and their therapeutic efficacy via upregulating the expression of Cx43. METHODS: MI was induced in 50 male Sprague-Dawley rats. The rats were randomized into five groups: MI group and four intervention groups, including the MSCs group, combined therapy group (MSCs+ pioglitazone), pioglitazone group and PBS group. Two weeks later, 5 × 10(6) MSCs labeled with PKH26 in PBS were injected into the infarct anterior ventricular free wall in the MSCs and combined therapy groups, and PBS alone was injected into the infarct anterior ventricular free wall in the PBS group. Pioglitazone (3 mg/kg/day) was given to the combined therapy and pioglitazone groups by oral gavage at the same time for another 2 weeks. Myocardial function and relevant signaling molecules involved were all examined thereafter. RESULTS: Heart function was enhanced after MSCs treatment for 2 weeks post MI. A significant improvement of heart function was observed in the combined therapy group in contrast to the other three intervention groups. Compared with the MSCs group, there was a higher level of PPAR-γ in the combined therapy group; Cx43 was remarkably increased in different regions of the left ventricle; TGF-β1 was decreased in the infarct zone and border zone. To the downstream signaling molecules, mothers against Smad proteins including Smad2 and Smad3 presented a synchronized alteration with TGF-β1; no differences of the expressions of ERK1/2 and p38 could be discovered in the left ventricular cardiac tissue. CONCLUSIONS: MSCs transplantation combined with pioglitazone administration improved cardiac function more effectively after MI. Activation of PPAR-γ could promote MSCs to express Cx43. Inhibition of TGF-β1/Smads signaling pathway might be involved in the process.
BACKGROUND: In this study, we hypothesized that activation of PPAR-γ enhanced MSCs survival and their therapeutic efficacy via upregulating the expression of Cx43. METHODS: MI was induced in 50 male Sprague-Dawley rats. The rats were randomized into five groups: MI group and four intervention groups, including the MSCs group, combined therapy group (MSCs+ pioglitazone), pioglitazone group and PBS group. Two weeks later, 5 × 10(6) MSCs labeled with PKH26 in PBS were injected into the infarct anterior ventricular free wall in the MSCs and combined therapy groups, and PBS alone was injected into the infarct anterior ventricular free wall in the PBS group. Pioglitazone (3 mg/kg/day) was given to the combined therapy and pioglitazone groups by oral gavage at the same time for another 2 weeks. Myocardial function and relevant signaling molecules involved were all examined thereafter. RESULTS: Heart function was enhanced after MSCs treatment for 2 weeks post MI. A significant improvement of heart function was observed in the combined therapy group in contrast to the other three intervention groups. Compared with the MSCs group, there was a higher level of PPAR-γ in the combined therapy group; Cx43 was remarkably increased in different regions of the left ventricle; TGF-β1 was decreased in the infarct zone and border zone. To the downstream signaling molecules, mothers against Smad proteins including Smad2 and Smad3 presented a synchronized alteration with TGF-β1; no differences of the expressions of ERK1/2 and p38 could be discovered in the left ventricular cardiac tissue. CONCLUSIONS: MSCs transplantation combined with pioglitazone administration improved cardiac function more effectively after MI. Activation of PPAR-γ could promote MSCs to express Cx43. Inhibition of TGF-β1/Smads signaling pathway might be involved in the process.
Authors: Jose A Morales-Garcia; Rosario Luna-Medina; Clara Alfaro-Cervello; Marta Cortes-Canteli; Angel Santos; Jose M Garcia-Verdugo; Ana Perez-Castillo Journal: Glia Date: 2011-02 Impact factor: 7.452
Authors: Jana Radosinska; Barbara Bacova; Vladimir Knezl; Tamara Benova; Jitka Zurmanova; Tomas Soukup; Petra Arnostova; Jan Slezak; Eva Gonçalvesova; Narcisa Tribulova Journal: J Hypertens Date: 2013-09 Impact factor: 4.844
Authors: Maryam Ahmadian; Jae Myoung Suh; Nasun Hah; Christopher Liddle; Annette R Atkins; Michael Downes; Ronald M Evans Journal: Nat Med Date: 2013-05-07 Impact factor: 53.440