سلمى صالح تركي الرداحي

الاسم الاول: 
سلمى
اسم العائلة: 
الرداحي
الدرجة العلمية: 
دكتوراة
مجال الدراسة: 
العلوم والتقنية
المؤسسة التعليمية: 
The University of Manchester

 

 

مجال التميز

تميز دراسي وبحثي 

 

 

البحوث المنشورة

 

البحث (1):

 

عنوان البحث:

Chronic Inflammation In Response To Injury: Retention Of Myeloid Cells In Injured Tissue Is Driven By Myeloid Cell Intrinsic Factors

رابط إلى البحث:

Click here 

تاريخ النشر:

28/01/2019

موجز عن البحث:

Chronic inflammation is a hallmark of impaired healing in a plethora of tissues, including skin, and is associated with aging and diseases such as diabetes. Diabetic chronic skin wounds are characterized by excessive myeloid cells that display an aberrant phenotype, partially mediated by stable intrinsic changes induced during hematopoietic development. However, the relative contribution of myeloid cell–intrinsic factors to chronic inflammation versus aberrant signals from the local environmental was unknown. Moreover, identification of myeloid cell intrinsic factors that contribute to chronic inflammation in diabetic wounds remained elusive. Here we show that Gr-1+CD11b+ myeloid cells are retained specifically within the presumptive granulation tissue region of the wound at a higher density in diabetic mice and associate with endothelial cells at the site of injury with a higher frequency than in nondiabetic mice. Adoptive transfer of myeloid cells demonstrated that aberrant wound retention is due to myeloid cell intrinsic factors and not the local environment. RNA sequencing of bone marrow and wound-derived myeloid cells identified Selplg as a myeloid cell intrinsic factor that is deregulated in chronic wounds. In vivo blockade of this protein significantly accelerated wound healing in diabetic mice and may be a potential therapeutic target in chronic wounds and other chronic inflammatory diseases. 

 

 

المؤتمرات العلمية:

 

المؤتمر (1):

 

عنوان المؤتمر:

Innate Immune Memory 2017 

تاريخ الإنعقاد:

14-16 March 2017 

مكان الإنعقاد:

Cambridge, UK

طبيعة المشاركة:

Poster presentation

عنوان المشاركة:

Protein Transduction Of Hoxa3 To Regulate NF-Kb Pathway And Hdacs/Hats In Diabetic Macrophages In Vitro 

ملخص المشاركة:

Cutaneous wound healing requires recruitment and differentiation of innate immune cells, particularly macrophages, from bone marrow cells for efficient tissue repair and regeneration. Patients with diabetes suffer from impaired wound healing that can lead to lower limb amputation. Prolonged chronic inflammation in both diabetic mouse models and human patients is associated with dysfunctional macrophages that fail to transit from pro-inflammatory phenotype (M1-like) to a pro-healing phenotype (M2-like). It has been demonstrated that diabetic environment induces aberrant macrophage phenotype that is partially mediated by stable intrinsic changes, but the underlying mechanisms have not yet been elucidated.

In this study, we have used bone marrow derived-macrophages isolated from diabetic and non-diabetic mice and either non activated (NA) or classically activated (CA) by LPS and INF-γ (M1-like) or Tnf activated (M1-like) to identify any changes in pro-inflammatory genes due to the diabetic environment. Crucially, we show that diabetes increases expression of many of the pro-inflammatory genes such as Tnf, Ccl2, and Nos2. Moreover, we have investigated deregulation in the expression of key M1/pro-inflammatory macrophage transcription factor NF-kB P65 and its natural inhibitor IKBα, both at the RNA and the protein level. Interestingly, this was also associated with misexpression of chromatin-remodelling enzymes, including Histone acetyltransferases (HATs) and Histone deacetylases (HDACs), which are important in regulating the transcription factor activity and histone modifications to facilitate gene transcription.

Our data suggest a possible link between chronic inflammation and elevated M1 polarization in diabetic wounds due to deregulation of NF-kB activity and histone acetylation enzymes.

In addition, we have used protein transduction of Hoxa3, a factor that is normally upregulated in wounds, but is repressed in diabetic wounds, to modulate the aberrant diabetic macrophage phenotype in vitro. Importantly, here we show that Hoxa3 induces macrophage maturation and inhibits the pro-inflammatory hyperpolarization, possibly by regulation of NF-kB, a critical regulator of inflammation, and its cofactor of HAT enzymes. Altogether our data suggest a potential for Hoxa3 protein transduction as a therapeutic.

 

 

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