Chromogranin A pathway: from pathogenic molecule to renal disease

Abstract

Background: Chromogranin A (CHGA) is an index granin protein critical for biogenesis and exocytotic release of catecholamine storage granules. It is elevated in plasma of patients with sympathetic over-activity and kidney dysfunction. Several CHGA polymorphisms are associated with hypertensive kidney disease. Previously, we unraveled the molecular mechanism by which CHGA expression is regulated in African Americans carrying a genetic variation associated with hypertensive chronic kidney disease (CKD).Method: Experimental CKD mouse model were created by 5/ 6th nephrectomy (Npx) using wild-type and ChgaÀ/À knockout mouse strains to delineate the role of CHGA in CKD.Result: Wild-type-Npx mice expressing Chga developed exacerbated azotemia and fibrosis as compared with their knockout-Npx counterparts. Gene expression profiling revealed downregulation of mitochondrial respiratory complexes genes consistent with maladaptive mitochondria in wild-type-Npx mice, contrasted to knockout-Npx. In healthy individuals, an inverse relationship between circulating CHGA levels and glomerular function was observed. In vitro, mesangial cells treated with CHGAtriggered nitric oxide release by a signaling mechanism involving scavenger receptor SR-A. The CHGA-treated and untreated mesangial cells displayed differential expression of cytokine, chemokine, complement, acute phase inflammatory and apoptotic pathway genes. Thus, build-up of plasma CHGA because of kidney injury served as an insult to the mesangial cells resulting in expression of genes promoting inflammation, fibrosis, and progression of CKD. Conclusion:These findings improve understanding of the role of elevated CHGA in the progression of CKD and reveal novel pathways that could be exploited for therapeutic strategies in hypertensive kidney disease.

A novel hypoxia-driven gene signature that can predict the prognosis of hepatocellular carcinoma

“…Consistent with previous studies, we found EGLN3 was increased in short time, while reduced in long time after hypoxic treatment. CHGA is a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins [ 39 ]. It is found in secretory vesicles of neurons and endocrine cells.…”

Serum chromogranin A correlated with albuminuria in diabetic patients and is associated with early diabetic nephropathy

“…However, serum CgA increases in renal failure more than creatinine and the other studied low-MW proteins, β2-MG (β2 microglobulin) and TATI (tumor-associated trypsin inhibitor) [ 12 ]. In animal experiments, an inverse correlation suggested a decrease in GFR with increasing plasma CgA concentration [ 30 ]. The study by Chen et al suggests CgA-stimulation of endothelial cell exocytosis of endothelin as a possible mechanism for regulation of renal function in health and disease [ 31 ].…”

Gene Signatures Associated with Temporal Rhythm as Diagnostic Markers of Major Depressive Disorder and Their Role in Immune Infiltration

“…Of these four biomarkers, CHGA has been reported to have a clear relationship with MDD [ 22 , 23 ]. CHGA is a protein-coding gene [ 23 ] and a member of the chromogranin/secretogranin family of neuroendocrine secretory proteins [ 24 ], which may influence the exocytotic release of neurotransmitters, including 5-hydroxytryptamine and dopamine—neurotransmitters that are involved in the sleep-wake cycle as well as implicated in depression. One study that investigated sectional CHGA levels in 40 male university students indicated an inverse association between salivary levels of CgA and the intensity of depressive symptoms [ 25 ].…”