Towards understanding pancreatic islet inflammation in MafA deficient mice
(2019) MOBN02 20182Degree Projects in Molecular Biology
- Abstract
- Maf transcription factors have pivotal roles in regulating beta cell function and development, and loss of MafA expression has been associated in inducing pro-inflammatory gene signature. This study assessed if the loss of MafA transcription factor expression contributes to the development of islet inflammation. Immunohistochemical analysis showed that 8 months old MafA deficient pancreata (MafA-/-) developed islet inflammation, which was previously only observed in 6 months old MafA-/-MafB+/-. RNA sequencing data revealed that expression of chemokines, innate and adaptive immune cell marker genes were induced in MafA deficient islets. Additionally, CD4+ T cells were the predominant cell types present in the inflammation associated with... (More)
- Maf transcription factors have pivotal roles in regulating beta cell function and development, and loss of MafA expression has been associated in inducing pro-inflammatory gene signature. This study assessed if the loss of MafA transcription factor expression contributes to the development of islet inflammation. Immunohistochemical analysis showed that 8 months old MafA deficient pancreata (MafA-/-) developed islet inflammation, which was previously only observed in 6 months old MafA-/-MafB+/-. RNA sequencing data revealed that expression of chemokines, innate and adaptive immune cell marker genes were induced in MafA deficient islets. Additionally, CD4+ T cells were the predominant cell types present in the inflammation associated with Maf deficient islets. We showed also that many extracellular matrix (ECM) genes were up-regulated in MafA-/- islets which may be a consequence of inflammatory processes. Moreover, we showed that Maf deficient mice displayed alterations in the pancreatic islet architecture, where α cells distribution is altered. (Less)
- Popular Abstract
- Pancreatic islet inflammation
Extreme high glucose (blood sugar) levels over time can damage the body's organs and give rise to diabetes Number of diabetic patients increases all over the world, making diabetes one of the major health challenging diseases. Sweden is one of the countries that have a high prevalence of diabetes.
The blood glucose level in our body is maintained with the help of two hormones called Insulin and glucagon. These two hormones are secreted by two different cell types within the hormone producing gland ¬(endocrine gland) in the pancreas known as beta and alpha cells. These two endocrine cells form a condensed cluster of cells called islets of Langerhans. When we eat food the blood glucose level increases,... (More) - Pancreatic islet inflammation
Extreme high glucose (blood sugar) levels over time can damage the body's organs and give rise to diabetes Number of diabetic patients increases all over the world, making diabetes one of the major health challenging diseases. Sweden is one of the countries that have a high prevalence of diabetes.
The blood glucose level in our body is maintained with the help of two hormones called Insulin and glucagon. These two hormones are secreted by two different cell types within the hormone producing gland ¬(endocrine gland) in the pancreas known as beta and alpha cells. These two endocrine cells form a condensed cluster of cells called islets of Langerhans. When we eat food the blood glucose level increases, this increase in blood glucose level stimulate insulin secretion from the pancreas allowing glucose to enter body cells and be used as a source of energy. However, when the blood glucose level decreases, glucagon hormone is secreted allowing the liver to release stored glucose, which causes blood sugar to rise.
There are two major types of diabetes, type 1 diabetes (T1D) and type 2 diabetes (T2D). In T2D, the pancreas produces insulin, but cells of the body are unable to use the insulin effectively. As a result glucose can’t enter the cells leading to high glucose levels. Unhealthy lifestyle and obesity are the major risk factors for developing T2D. However, T1D starts when the body's own immune cells attack causing inflammation and destroy the insulin-producing cells in the pancreas leading to low or no insulin production. T1D is an autoimmune disease and it is common among children and adolescents. Disorders of the genetic components that contribute to normal cell function, associated with the development of diabetes. Hence, understanding the genetic composition of the disease will aid to improve diagnosis and treatment of diabetes.
In this project, we studied the role of two genetic factors MafA and MafB in pancreatic islet inflammation. MafA and MafB are important genes for beta cells development and function. We investigated if the loss of MafA and MafB enhances islet inflammation. Our work showed that absence of MafA and/or MafB enhance the development of autoimmune response (immune cells) against the pancreatic islets and they were mainly T cells (a type of lymphocyte). These autoimmune responses may lead to T1D.
Master’s Degree Project in Molecular Biology, 45 credits 2019
Department of Biology, Lund University
Advisor: Isabella Artner &Tania Singh (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/8989980
- author
- Bsharat, Sara
- supervisor
- organization
- course
- MOBN02 20182
- year
- 2019
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 8989980
- date added to LUP
- 2019-07-04 11:30:26
- date last changed
- 2019-07-04 11:30:26
@misc{8989980,
abstract = {{Maf transcription factors have pivotal roles in regulating beta cell function and development, and loss of MafA expression has been associated in inducing pro-inflammatory gene signature. This study assessed if the loss of MafA transcription factor expression contributes to the development of islet inflammation. Immunohistochemical analysis showed that 8 months old MafA deficient pancreata (MafA-/-) developed islet inflammation, which was previously only observed in 6 months old MafA-/-MafB+/-. RNA sequencing data revealed that expression of chemokines, innate and adaptive immune cell marker genes were induced in MafA deficient islets. Additionally, CD4+ T cells were the predominant cell types present in the inflammation associated with Maf deficient islets. We showed also that many extracellular matrix (ECM) genes were up-regulated in MafA-/- islets which may be a consequence of inflammatory processes. Moreover, we showed that Maf deficient mice displayed alterations in the pancreatic islet architecture, where α cells distribution is altered.}},
author = {{Bsharat, Sara}},
language = {{eng}},
note = {{Student Paper}},
title = {{Towards understanding pancreatic islet inflammation in MafA deficient mice}},
year = {{2019}},
}