Abstract: SA-PO065
Neuro-Immune Cross-Talk in Pathophysiology of AKI
Session Information
- AKI: Mechanisms - Primary Injury and Repair - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Puri, Sanjeev, Panjab University, Chandigarh, India
- Puri, Veena, Panjab University, Chandigarh, India
- Gupta, Aprajita, Panjab University, Chandigarh, India
Background
Acute kidney injury is a heterogeneous syndrome characterized by inflammation, decrease in glomerular filtration rate, vascular modulation, oliguria and swing in nervous system. Its progression is mediated by cytokines production, neuro-molecules and infiltration of immune cells into kidneys and other organs including brain. Lead molecule, TNF-α aids in the recruitment & activation of immune response. The neuropeptide calcitonin gene-related peptide (CGRP) has been significantly observed in pain pathways, hemodynamic and nerve signal modulation in AKI. The interdependent mediation of immune molecules and neuropeptide during AKI further point to the progression of pain pathways that still remains unexplored in AKI.
Methods
A systems biology approach was used to find neuro-inflammatory molecules of AKI by employing in-silico retrieval of AKI genes and investigation of their role in mouse model. The neuro-inflammatory genes in AKI and the respective signalling pathways were searched by PANTHER, GENOMATIX and Target Explorer. Common interactors between TNF and CGRP were expedited by STRING and CYTOSCAPE. The AKI was induced in male Balb/c mice through an intraperitoneal injection of folic acid (250 mg/kg). Kidneys and brains were harvested and expression of CGRP and TNF-alpha, TRPV1, PTGER4 and CGRP receptor genes were analyzed by quantitative real-time PCR analysis. Immuno-histology of kidney and brain and Serum ELISA were employed to study the CGRP and TNFα protein expression. The changes in BBB were evaluated by Evan’s blue estimation.
Results
The in-silico search retrieved a list of 49 genes which participate in neuro-immune axis of AKI. KEGG pathway analysis revealed that most of these communicators converse through the calcium signalling pathways. With progression of injury mRNA expression of CGRP, TNF- α and other genes was found modulated. The variation in expression was also reflected by immuno-histology in kidney and brain. The serum CGRP and TNF were also modulated in similar fashion as estimated by ELISA. The changes in the cell architecture of brain and the changes in BBB evidence the kidney cross talk with brain.
Conclusion
The study unveils the route of the communication between CGRP and TNF on neuro-immune axis. Most of the mediators signal through calcium mediated pathways leading to pain and pointing towards one of the pilot routes between them.
Funding
- Government Support - Non-U.S.