Bioinformatics Unmasks the Maneuverers of Pain Pathways in Acute Kidney Injury

Abstract

Acute Kidney injury (AKI) is one of the leading health concerns resulting in accumulation of nitrogenous as well as non-nitrogenous wastes in body and characterised by a rapid deterioration in kidney functions. Besides the major toll from the primary insult in the kidney, consequential extra-renal secondary insults endowed with the pathways of inflammatory milieu often complicates the disease outcome. Some of the known symptoms of AKI leading to clinical reporting are fatigue, loss of appetite, headache, nausea, vomiting, and pain in the flanks, wherein proinflammatory cytokines have been strongly implicated in pathogenesis of AKI and neuro-inflammation. Taking in account these clues, we have tried to decode the neuro-inflammation and pain perception phenomenon during the progression of AKI using the pathway integration and biological network strategies. The pathways and networks were generated using bioinformatics software viz. PANTHER, Genomatix and PathVisio to establish the relationship between immune and neuro related pathway in AKI. These observations envisage a neurol-renal axis that is predicted to involve calcium channels in neuro-inflammatory pathway of AKI. These observations, thus, pave a way for a new paradigm in understanding the interplay of neuro-immunological signalling in AKI.

Bioinformatics Approach to Investigate the Genes Manifesting Alopecia Areata

“…Bioinformatics tools have panned a way greatly in exploring the new vistas for nding biomarkers and targets for various diseases (7)(8)(9). In the present study, GEO the genomic data repository was used for data sourcing.…”

Multidimensional Data Integration Identifies Tumor Necrosis Factor Activation in Nephrotic Syndrome: A Model for Precision Nephrology

“…Because multiple lines of evidence converged in TNF, we sought an approach to assess intrakidney activation of TNF non-invasively for patient stratification. Using a rich knowledge base [36][37][38] , we extracted a set of 272 intra-renal transcript as a readout of TNF activity via its downstream regulated genes (supplementary table s2). The score was calculated for each patient biopsy profile 17,[39][40][41] , and evaluated across the cohorts (Figure 4A).…”

Neuroimmune Mechanisms in Signaling of Pain During Acute Kidney Injury (AKI)

“…The immune cells have the receptor for CGRP. CGRP and TNF-α together demonstrate a bi-directional relationship between immune and nervous system (1,113). There has been an inconclusive debate about CGRP's regulation by TNF-α.…”

“…Kidney is a calcium-sensing organ that regulates the homeostasis of urinary and extracellular Ca 2+ in body (130). Kidneys possess calcium sensing receptors (CaSR) across entire length of the nephron and thick ascending limb (131) and establish regulation of calciotropic hormones and renal feedback loop that incorporates the actions of the CaSR, parathyroid hormone (PTH) and calcitriol to provide rapid and local control of Ca 2+ and Pi homeostasis (1,132). AKI leads to rise in free intracellular calcium after AKI (Figure 2).…”

“…The cellular crosstalk by these molecules together with different cellular mechanisms that afflict AKI and thereafter its neurological impairments such as nociception are incompletely understood. In this quest, we have recently reported the putative genes that participate in neuroimmune interactions during pain perception of AKI (1). Further enriching our knowledge of neuro-immune interaction in renal injury could lead to new therapies for inflammation induced pain and other neurological impairments.…”