Impaired TGF-β signaling and a defect in resolution of inflammation contribute to delayed wound healing in a female rat model of type 2 diabetes

2011 ◽  
Vol 7 (11) ◽  
pp. 3006 ◽  
Author(s):  
Fahd Al-Mulla ◽  
Samuel J. Leibovich ◽  
Issam M. Francis ◽  
Milad S. Bitar
Keyword(s):  
Type 2 Diabetes ◽  
Wound Healing ◽  
Rat Model ◽  
Female Rat ◽  
Delayed Wound Healing ◽  
Resolution Of Inflammation

scholarly journals Evaluation of the In Vitro Damage Caused by Lipid Factors on Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence

2020 ◽  
Vol 21 (14) ◽  
pp. 5045
Author(s):  
Istvan Kovanecz ◽  
Robert Gelfand ◽  
Sheila Sharifzad ◽  
Alec Ohanian ◽  
William DeCastro ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Urinary Incontinence ◽  
Stem Cell ◽  
Stress Urinary Incontinence ◽  
Rat Model ◽  
Male Rats ◽  
Female Stress Urinary Incontinence ◽  
Female Rat

Human stem cell therapy for type 2 diabetes/obesity (T2D/O) complications is performedwith stem cell autografts, exposed to the noxious T2D/O milieu, often with suboptimal results.We showed in the Obese Zucker (OZ) rat model of T2D/O that when their muscle-derived stemcells (MDSC) were from long-term T2D/O male rats, their repair ecacy for erectile dysfunctionwas impaired and were imprinted with abnormal gene- and miR-global transcriptional signatures(GTS). The damage was reproduced in vitro by short-term exposure of normal MDSC to dyslipidemicserum, causing altered miR-GTS, fat infiltration, apoptosis, impaired scratch healing, and myostatinoverexpression. Similar in vitro alterations occurred with their normal counterparts (ZF4-SC) fromthe T2D/O rat model for female stress urinary incontinence, and with ZL4-SC from non-T2D/O leanfemale rats. In the current work we studied the in vitro eects of cholesterol and Na palmitate aslipid factors on ZF4-SC and ZL4-SC. A damage partially resembling the one caused by the femaledyslipidemic serum was found, but diering between both lipid factors, so that each one appears tocontribute specifically to the stem cell damaging eects of dyslipidemic serum in vitro and T2D/Oin vivo, irrespective of gender. These results also confirm the miR-GTS biomarker value forMDSC damage.

Abstract 169: Type 2 Diabetes-Induced Hematopoietic Stem Cell Oxidant Stress Attenuates the Differentiation, Skews M1/M2 Specification of Monocytes/Macrophages and Delays Wound Healing in db/db Mice

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Jinglian Yan ◽  
Guodong Tie ◽  
Shouying Wang ◽  
Louis Messina
Keyword(s):  
Type 2 Diabetes ◽  
Wound Healing ◽  
Wound Closure ◽  
Oxidant Stress ◽  
M2 Macrophage ◽  
Delayed Wound Healing ◽  
Hematopoietic Stem ◽  
M1 Macrophage ◽  
M2 Phenotype

Rationale After recruitment to wounds, monocytes differentiate into macrophages which play a central role in all stages of wound healing. Wound healing is significantly delayed in type 2 diabetes and it is related to macrophage specification into M1/M2 phenotype, but the mechanism remains unknown. Objective This study tested the hypothesis that type 2 diabetes induces hematopoietic stem cells (HSCs) oxidant stress that reduces their differentiation towards monocytes and skews the specification of M1/M2 phenotype, thereby causing delayed wound healing. Methods and Results HSCs were sorted from bone marrow of WT and db/db type 2 diabetic mice. DCF staining showed significant oxidant accumulation in HSCs from db/db mice which was reversed by the antioxidant, N-acetylcysteine (NAC). Bone marrow monocyte concentration (FACS analysis of cell surface markers f4/80, cd14 and cd115) was significantly lower in db/db mice than in WT mice. NAC also reversed the reduced differentiation towards monocyte. Wound closure rate was significantly delayed in db/db mice. Macrophages were isolated from wounds and their concentration and M1/M2 phenotype were quantified by flow cytometry. During the inflammatory phase of wound healing, macrophage concentration was decreased and the proportion of M1 macrophage was lower in db/db mice than in WT mice. During new tissue formation phase , macrophage concentration was decreased and the proportion of M2 macrophage was lower, but M1 macrophage was higher in db/db mice than in WT mice. During tissue remodeling phase , macrophage concentration was increased and M1 macrophage remained higher in db/db mice, but no difference was observed in the proportion of M2 macrophage. The reduced differentiation of HSCs towards monocytes and the delayed wound closure phenotype of db/db mice could be transferred to WT mice by transplanting db/db HSCs into lethally irradiated WT mice. Conclusion Type 2 diabetes-induced HSC oxidant stress impairs HSC differentiation towards monocytes, skews the M1/M2 specification of macrophages and thereby accounts for the delayed wound healing. Type 2 diabetes-induced HSC oxidant stress may be a heretofore unrecognized critical regulator of dysinflammation in type 2 diabetes.

Effect of Metformin on Periimplant Wound Healing in a Rat Model of Type 2 Diabetes

2014 ◽  
pp. 1 ◽  
Author(s):  
Kimberly Ann S. Inouye ◽  
Frederick C. Bisch ◽  
Mohammed E. Elsalanty ◽  
Ibrahim Zakhary ◽  
Rania M. Khashaba ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Wound Healing ◽  
Rat Model

1045: Pioglitazone Ameliorates Penile Corpora Veno-Occlusive Dysfunction (CVOD) in a Rat Model of Type 2 Diabetes

2005 ◽  
Vol 173 (4S) ◽  
pp. 283-284
Author(s):  
Istvan Kovanecz ◽  
Monica G. Ferrini ◽  
Hugo H. Davila ◽  
Jacob Rajfer ◽  
Nestor F. Gonzalez-Cadavid
Keyword(s):  
Type 2 Diabetes ◽  
Rat Model

scholarly journals Role of TLR4/MyD88/NF-κB signaling in heart and liver-related complications in a rat model of type 2 diabetes mellitus

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199759
Author(s):  
Jiajia Tian ◽  
Yanyan Zhao ◽  
Lingling Wang ◽  
Lin Li
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Rat Model ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Primary Response ◽  
Monocyte Chemoattractant Protein 1

Aims To analyze expression of members of the Toll-like receptor (TLR)4/myeloid differentiation primary response 88 (MyD88)/nuclear factor (NF)-κB signaling pathway in the heart and liver in a rat model of type 2 diabetes mellitus (T2DM). Our overall goal was to understand the underlying pathophysiological mechanisms. Methods We measured fasting blood glucose (FBG) and insulin (FINS) in a rat model of T2DM. Expression of members of the TLR4/MyD88/NF-κB signaling pathway as well as downstream cytokines was investigated. Levels of mRNA and protein were assessed using quantitative real-time polymerase chain reaction and western blotting, respectively. Protein content of tissue homogenates was assessed using enzyme-linked immunosorbent assays. Results Diabetic rats had lower body weights, higher FBG, higher FINS, and higher intraperitoneal glucose tolerance than normal rats. In addition, biochemical indicators related to heart and liver function were elevated in diabetic rats compared with normal rats. TLR4 and MyD88 were involved in the occurrence of T2DM as well as T2DM-related heart and liver complications. TLR4 caused T2DM-related heart and liver complications through activation of NF-κB. Conclusions TLR4/MyD88/NF-κB signaling induces production of tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1, leading to the heart- and liver-related complications of T2DM.

The effects of apelin treatment on a rat model of type 2 diabetes

2015 ◽  
Vol 60 (1) ◽  
pp. 94-100 ◽  
Author(s):  
Raziye Akcılar ◽  
Sebahat Turgut ◽  
Vildan Caner ◽  
Aydın Akcılar ◽  
Ceylan Ayada ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Rat Model
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