Sitagliptin inhibits EndMT in vitro and improves cardiac function of diabetic rats through the SDF-1α/PKA pathway
Authors: Y Wu
J-H Zhang
M Xu
H Bao
Journal: European Review for Medical and Pharmacological Sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Sitagliptin; Endothelial-mesenchymal transition; Cardiac function; Diabetes mellitus; Sprague Dawley rats
Affiliations: Department of Endocrine, Shanxian Central Hospital, Heze, Shandong, China. .

Abstract:  Objective: The aim of this paper was to study sitagliptin in improving the endothelial-mesenchymal transition (EndMT) of human aortic endothelial cells (HAECs) and cardiac function of rats with diabetes mellitus (DM) and its possible pathway. Materials and methods: Sprague Dawley (SD) rats were divided into control group, DM group and sitagliptin group. The myocardial contraction and relaxation functions of rats in each group were observed via echocardiography. The changes in cardiac structure and fiber were observed via hematoxylin-eosin (HE) staining, Masson staining and Sirius red staining. The immunohistochemical assay was performed to observe the expressions of α-smooth muscle actin (α-SMA) and VE-cadherin in HAECs; the expression of reactive oxygen species (ROS) in HAECs was detected using the fluorescence probe. Moreover, the expressions of transforming growth factor-β1 (TGF-β1), phosphorylated-protein kinase A (p-PKA), PKA and extracellular signal-regulated kinase (ERK) were observed via Western blotting. Results: Sitagliptin could improve the myocardial contraction and relaxation functions in diabetic rats and EndMT and ROS production in HAECs. In the DM group, the expression of Glucagon-like peptide-1 (GLP-1) was decreased, while the expression of stromal-derived factor-1α (SDF-1α) was decreased and the expressions of downstream PKA/ERK pathway and TGF-β1 were increased. The above changes could be reversed by sitagliptin. Conclusions: Sitagliptin can reverse the EndMT in HAECs as well as the cardiac function in diabetic rats through the SDF-1α/PKA pathway. 

Retracted: No

PubPeer comments:
 Above: Figure 2A.  Sitagliptin improves the myocardial function of rats. A, M-mode echocardiogram of rats in each group . Below: Figure 2A from [Zhang et al (2019)] .  Up-regulation of miR-548c-3p improved cardiac function after infarction. A, Representative transthoracic M-mode echocardiograms from each group. . I have concerns. ![file] , 
  Figure 4. .. B, ROS expression in HAECs. HG panel. ![file] , 
 *[left]* Fig 4C,  Expression of ERK and TGF-u03b21 in HAECs in each group. Obtained from *[right]* Fig 1A,  MAPK Signaling Drives Inflammation in LPS-Stimulated Cardiomyocytes: The Route of Crosstalk to G-Protein-Coupled Receptors ([Frazier et al 2012] ). ![file] , 
 *[left]* Fig 2C. Images were taken from *[right]* Fig 2E of  All-Trans Retinoic Acid Induces TGF-u03b22 in Intestinal Epithelial Cells via RhoA- and p38u03b1 MAPK-Mediated Activation of the Transcription Factor ATF2 ([Namachivayam et al 2015] ). ![file] , 
 *[left]* Fig 3A. Panels are pilfered from *[right]* Fig 4A of  Cytokine-Like 1 Regulates Cardiac Fibrosis via Modulation of TGF-u03b2 Signaling ([Kim et al 2016] ). Here flipped through 90 deg for ease of comparison. ![file] , 
 #1 *[above]* Fig 2A,  M-mode echocardiogram of rats in each group. ... Doppler image of mitral flow in each group. Purloined from *[below]* Fig 3A of  Advanced glycation end product cross-link breaker attenuates diabetes-induced cardiac dysfunction by improving sarcoplasmic reticulum calcium handling ([Kranstuber et al 2012] ).  A representative paired M-mode echocardiograms (top panel) and transmitral Doppler flow (bottom panel) at 8 weeks of treatment in control (Con), untreated diabetic (DX), and treated diabetic (DX-ALT) groups. IVS, interventricular septum; LVPW, left ventricular posterior wall; RV, right ventricle; IVRT: isovolumic relaxation time . ![file] , 
 *[left]* Fig 2B. Sources include *[right]*- - Fig 3c (C1 row) from  Early administration of trimetazidine attenuates diabetic cardiomyopathy in rats by alleviating fibrosis, reducing apoptosis and enhancing autophagy ([Zhang et al 2016] ); and - Fig 4A from  Prohibitin overexpression improves myocardial function in diabetic cardiomyopathy ([Dong et al 2015] ). ![] ,