McMaster University

Medical Sciences
Graduate Program

Scope of Search

 

Joan Krepinsky

Joan Krepinsky

 

B.Sc., MD, MSc, FRCPC
Professor

Research Interests

Our laboratory studies mechanisms involved in the development and progression of chronic kidney failure secondary to hypertension and diabetes. The focus is on kidney (mesangial) cell signaling in response to diabetic and profibrotic stimuli (high glucose, transforming growth factor  (TGF) family members), with a specific focus on pathways important in extracellular matrix production and hence kidney/glomerular fibrosis. Results are tested in relevant animal models.

 


 

We are specifically investigating the following:

  1. Role of caveolae in mechanical stretch-induced activation of the small GTPase RhoA. We have previously shown RhoA to regulate production of the matrix protein fibronection
  2. How RhoA might be involved in high glucose- mediated fibronectin production
  3. Role of the protein kinase Akt in production of collagen in response to high glucose1. The role of activin A, a TGF family member, in diabetic and hypertensive kidney disease. A collaborative project is investigating how the activin A protein inhibitor follistatin lowers blood pressure and what effects it has on vessel structure and function in hypertensive models. Understanding how activin A contributes to the profibrotic effects of TGF1 is also being studied in vitro and in vivo.
    2. The microRNA miR299a-5p can increase endogenous levels of antifibrotic follistatin and potentially other antifibrotic proteins. We are assessing its effects in cell culture and in diabetic and hypertensive animal models.
    3. How the cell surface relocalization of the endoplasmic reticulum chaperone GRP78 mediates high glucose-induced profibrotic responses, and whether its targeting in vivo protects against diabetic kidney disease.
    4. How the adaptor protein LASP1 contributes to fibrosis in response to high glucose and whether its absence protects against diabetic kidney disease.

     


Both in vitro and in vivo approaches are used. Methodologies include cell culture, protein analysis (electrophoresis, kinase assays, cell fractionation), qRT-PCR, cloning, promoter studies, immunofluorescence, DNA transfection/infection and ELISA. Animal models (rats, mice) include various diabetic, hypertensive and chronic kidney disease models.

Contact

McMaster University
St. Joseph's Healthcare

telephone: 905-522-1155 ext. 34991
email: krepinj@mcmaster.ca

 

Program Area

Blood & Vasculature

 

Research Focus

Hypertensive kidney disease, Diabetic kidney disease, Matrix Upregulation, Mesangial cell signaling

Selected Publications

1. Van Krieken R, Mehta N, Wang T, Zheng M, Li R, Go B, Ayaub E, Ask K, Paton JC, Paton AW, Austin RC, Krepinsky JC. Cell surface expression of 78-kDa glucose regulated protein (GRP78) mediates diabetic nephropathy. J Biol Chem 294(19):7755, 2019.

2. Mehta N, Zhang D, Li R, Wang T, Gava A, Parthasarathy P, Gao B, Krepinsky JC. Caveolin-1 regulation of Sp1 controls production of the antifibrotic protein follistatin in kidney mesangial cells. Cell Commun Signal 17(1):37, 2019.

3. Mehta N, Gava AL, Zhang D, Gao B, Krepinsky JC. Follistatin protects against glomerular mesangial cell apoptosis and oxidative stress to ameliorate chronic kidney disease. Antioxid Redox Signal 31(8):551-571, 2019.

4. Zhang D, Gava AL, Van Krieken R, Mehta N, Li R, Gao B, Desjardins EM, Steinberg GR, Hawke T, Krepinsky JC. The caveolin-1 regulated protein follistatin protects against diabetic kidney disease. Kidney Int 96(5):1134-1149, 2019.

5. Mehta N and Krepinsky JC. The emerging role of activins in renal disease. Curr Opin Nephrol Hypertension 29(1):136-144, 2020.