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Sexual dimorphisms and role of cGAS-STING Pathway in T2DN rats
Summary Data Summary
Applicant Staruschenko, Alexander
E-Mail Address staruschenko@usf.edu
Project Title Sexual dimorphisms and role of cGAS-STING Pathway in T2DN rats
CBU ID 20AU4119
External SubContract ID 32307-98
Diabetic Complication Nephropathy
Funding Program Group Pilot & Feasibility [PF2020]
Abstract Diabetes and its renal complications are becoming an epidemic in the U.S.
population. Diabetic kidney disease (DKD) is the leading cause of chronic renal
pathology and, therefore, is the subject of major research efforts. DKD is one
of the primary missions of the National Institute of Diabetes and Digestive and
Kidney. Importantly, as described on the Ö÷²¥ÓÕ»ó website, diabetic complications
manifest themselves differently between men and women. Understanding the
molecular underpinnings of these manifestations is critical to designing
tailored therapeutic approaches. This proposal is focused on sex differences in
the progression of DKD. To explore the sexual dimorphisms in the development of
DKD, we propose to use here type 2 diabetic nephropathy (T2DN) rats. Type 2
diabetes in T2DN rats is accompanied by renal histologic abnormalities that are
characteristic of DN, similar to clinical observations in human patients. T2DN
model was also successfully used to evaluate several drugs and signaling
pathways supporting its use as a model of DKD. This project aims to determine
phenotypic characteristics of DKD progression related to the sex difference in
T2DN rats and identify potential mechanisms responsible for renal injury. Our
preliminary data suggests the functional divergence between the kidney injury
and DKD progression in male and female T2DN rats, similar to clinical
observations in human patients. Aim 1 will further explore these functional and
structural differences between male and female T2DN rats using gonadectomized
animals. Furthermore, our pilot studies have revealed that the cyclic GMP -AMP
synthase (cGAS) / Stimulator of interferon genes (STING) signaling pathway is
differently regulated between male and female T2DN rats. Role of cGAS -STING
pathway in multiple regulatory mechanisms, including renal inflammation, was
recently reported, and we hypothesize that this pathway contributes towards the
progression of DKD and sexual dimorphism. Therefore, aim 2 will provide
mechanistic insight about potential mechanisms of sex differences in type 2 DN.
A combination of in vivo and ex vivo studies will be used to address the
following Specific Aims: Aim 1) To characterize the sexual dimorphisms in the
progression of DKD in T2DN rats; and Aim 2) To define the contribution of the
cGAS-STING signaling pathway in the progression of DKD and its contribution to
sex difference.
Application PDF Application Research Plan
Status Contract Executed
Key Personnel Oleg Palygin, PhD
Salary Total Costs 49933
Supply Total Costs 13669
Equipment Total Costs 0
Travel/Other Total Costs 500
Direct Costs 64102
Indirect Costs Proposed 35897
Total Costs Proposed 99999
Total Costs Approved 99999
Start Date 11/1/2020
End Date 6/20/2022
IFO Name Thompson, Katherine
IFO E-Mail Address kmthompson@mcw.edu
IACUC/IRB No. AUA1061
IACUC/IRB Institution Medical College of Wisconsin
Entity ID No.
Report Request Date 6/20/2022
T1D NO
TypeCount
Invoices 2
Progress Reports 1
Data Submission


Invoices
UrlCBU IDExternal IDInstitutionDateDirectIndirectInvoiceBalancePDF
  View  20AU411932307-98Medical College of Wisconsin9/30/2022$33,037.36$16,353.49$49,390.85$35,795.00View PDF
  View  20AU411932307-98Medical College of Wisconsin5/30/2022$9,908.46$4,904.69$14,813.15$35,795.00View PDF
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