Why is there a higher female prevalence for PAH?
BMPR2 Gene Domain
Hypothesis:
BMPR2 gene expression is repressed by higher levels of estrogen in the blood
Aim 1
To investigate how BMPR2 gene is expressed at different levels in females and males in our in vitro study using adult human adipocytes
WHY?
To identify whether different level of estrogen causes different level of BMPR2 expression
To identify whether different level of estrogen causes different level of BMPR2 expression
HOW?
My first aim is investigating how BMPR2 gene is expressed at different levels in females and males in our in vitro study using adult human adipocytes, one is with PAH and the other is just normal control. The reason I am doing this is to see whether different level of estrogen cause different level of BMPR2 expression and if yes, how.
First of all, I will culture females and males human adipocytes over one week. Then I will use DNA microarray to measure the level of BMPR2 gene expression and to identify whether BMPR2 gene is expressed as proteins in the cell. After it, I will use Western Blot to detect the difference of BMPR2 protein expression level in vitro between females and males.
First of all, I will culture females and males human adipocytes over one week. Then I will use DNA microarray to measure the level of BMPR2 gene expression and to identify whether BMPR2 gene is expressed as proteins in the cell. After it, I will use Western Blot to detect the difference of BMPR2 protein expression level in vitro between females and males.
Expectation:
Higher expression of estrogen in the blood in females represses the expression of BMPR2
Aim 2
To determine if the level of estrogen in the blood regulates the expression of BMPR2
WHY?
To nail down whether different level of estrogen causes different level of BMPR2 expression
To nail down whether different level of estrogen causes different level of BMPR2 expression
HOW?
My second aim is to determine whether the level of estrogen in the blood regulates the expression of BMPR2. The reason I am doing it is to make sure whether different level of estrogen causes different level of BMPR2 expression. First of all, I will inject different concentration of estrogen to the wild type of female mice. Such as no injection, inject normal amount, twice, and triple. After these, I will use tap-tag and mass-spec to determine whether estrogen and BMPR2 interact each other or not. Then, I will use immunoprecipitation or pull-down assay to confirm the interaction.
Expectation:
High concentrations of estrogen lead to the repression of BMPR2 expression by interacting with its potential partners
Conclusion
I conclude that high level of estrogen expression causes the repression of BMPR2 expression
Future Directions
For the first future direction,
by determining the levels of estrogen in the blood in females from birth to death,
I want to see whether the level of BMPR2 gene expression is changed or not
by determining the levels of estrogen in the blood in females from birth to death,
I want to see whether the level of BMPR2 gene expression is changed or not
For the second future direction,
since PAH is a disease related with narrowed arteries,
I want to see whether salty food can cause the repression of BMPR2 gene expression.
For this, I will feed different diet such as high salt and low salt on wilt type of mice
and see whether the level of BMPR2 gene expression is changed or not.
since PAH is a disease related with narrowed arteries,
I want to see whether salty food can cause the repression of BMPR2 gene expression.
For this, I will feed different diet such as high salt and low salt on wilt type of mice
and see whether the level of BMPR2 gene expression is changed or not.
Further research for the second future direction
Mouse (Rattus norvegicus) BMPR2 - Hypertension: Heart
DNA microarray data of Mouse BMPR2 - Hypertension: Heart
Analysis
According to the clinical data, females are diagnosed with PAH twice higher than males. However, it is unclear why there is a higher female prevalence for PAH. Therefore, I hypothesize that BMPR2 gene expression is repressed by higher levels of estrogen in the blood.
My first aim is investigating how BMPR2 gene is expressed at different levels in females and males in our in vitro study using adult human adipocytes, one is with PAH and the other is just normal control. And I expect that higher expression of estrogen in the blood in females represses the expression of BMPR2.
My second aim is to determine if the level of estrogen in the blood regulates the expression of BMPR2. And I expect that high concentration of estrogen lead to the repression of BMPR2 expression by interacting with its potential partners such as BMP proteins which is related to Estrogen. Therefore, I conclude that high level of estrogen expression causes the repression of BMPR2 expression.
For the first future direction, by determining the level of estrogen in the blood in females from birth to death, I want to identify whether BMPR2 expression level is changed or not and if yes, how.
For the second future direction, since PAH is a disease related with narrowed arteries, I want to see whether salty food can cause the repression of BMPR2 gene expression or not. For this, I will feed different diet, high salt and low salt, on wilt type of mice and see whether the level of BMPR2 gene expression is changed or not. To test the second future direction, GEO (Gene Expression Omnibus) is used to get Mouse (Rattus norvegicus) BMPR2 microarray data. The data shows that genes are more expressed in the congenic strain than Dahl salt-sensitive strain. For the detail explanations, further research would be needed.
My first aim is investigating how BMPR2 gene is expressed at different levels in females and males in our in vitro study using adult human adipocytes, one is with PAH and the other is just normal control. And I expect that higher expression of estrogen in the blood in females represses the expression of BMPR2.
My second aim is to determine if the level of estrogen in the blood regulates the expression of BMPR2. And I expect that high concentration of estrogen lead to the repression of BMPR2 expression by interacting with its potential partners such as BMP proteins which is related to Estrogen. Therefore, I conclude that high level of estrogen expression causes the repression of BMPR2 expression.
For the first future direction, by determining the level of estrogen in the blood in females from birth to death, I want to identify whether BMPR2 expression level is changed or not and if yes, how.
For the second future direction, since PAH is a disease related with narrowed arteries, I want to see whether salty food can cause the repression of BMPR2 gene expression or not. For this, I will feed different diet, high salt and low salt, on wilt type of mice and see whether the level of BMPR2 gene expression is changed or not. To test the second future direction, GEO (Gene Expression Omnibus) is used to get Mouse (Rattus norvegicus) BMPR2 microarray data. The data shows that genes are more expressed in the congenic strain than Dahl salt-sensitive strain. For the detail explanations, further research would be needed.
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References
- Header Image: http://www.realproperty.pk/blog/wp-content/uploads/2014/02/past-present-future-real-estate-in-pakistan.jpg
- Getting Started. (n.d.). NCBI. Retrieved May 19, 2014, from http://www.ncbi.nlm.nih.gov/geo/