Research

Life Sciences & Biotechnology

Title :

Characterizing the role of Kupffer cell Gi signaling pathway in the pathogenesis of non-alcoholic steatohepatitis

Area of research :

Life Sciences & Biotechnology

Principal Investigator :

Dr. shanu jain, Indian Institute Of Technology Kanpur (IITK), Uttar Pradesh

Timeline Start Year :

2024

Timeline End Year :

2026

Contact info :

Equipments :

Details

Executive Summary :

Obesity and Type 2 Diabetes (T2D) are a global pandemic, with India emerging as the "diabetic capital" of the world. By 2030, approximately 98 million Indians will be diabetic, accounting for over one-sixth of the world population. The liver is a critical metabolic organ that regulates glucose, lipid, and energy metabolism. Kupffer cells (KC) are liver resident macrophages that regulate hepatic inflammatory responses and glucose and lipid metabolism. Dysregulation of KC function can lead to liver metabolic disorders such as NAFLD, NASH, and liver fibrosis. The role of GPCR signaling pathway in regulating KC functions has been sparsely explored. The study hypothesizes that KC-Gi signalling may play a critical role in the pathogenesis of NASH. A mouse model expressing Gi inhibitor-PTX specifically in KC will be employed to decipher molecular mechanisms of Gi signalling. The effects of GiKO on KC function and NASH will be deciphered through physiological evaluation, pathological evaluation, biochemical evaluation, and molecular evaluation. The study will also study the crosstalk of KC lacking Gi signalling with primary hepatocytes, which has significance in the pathogenesis of liver disorders. No FDA-approved drug exists for the treatment of NASH, and understanding the role of Gi signalling in regulating KC function may help develop novel pharmacological strategies aimed at altering KC-Gi signalling for NASH treatment. Future work could involve synthesizing drug candidates targeting Gi pathways tested in in-vitro and in-vivo models of NASH.

Total Budget (INR):

32,70,344

Organizations involved