Molecular characterization of the transition from acute to chronic kidney injury following ischemia/reperfusion

Abstract

Though an acute kidney injury (AKI) episode is associated with an increased risk of chronic kidney disease (CKD), the mechanisms determining the transition from acute to irreversible chronic injury are not well understood. To extend our understanding of renal repair, and its limits, we performed a detailed molecular characterization of a murine ischemia/reperfusion injury (IRI) model for 12 months after injury. Together, the data comprising RNA-sequencing (RNA-seq) analysis at multiple time points, histological studies, and molecular and cellular characterization of targeted gene activity provide a comprehensive profile of injury, repair, and long-term maladaptive responses following IRI. Tubular atrophy, interstitial fibrosis, inflammation, and development of multiple renal cysts were major long-term outcomes of IRI. Progressive proximal tubular injury tracks with de novo activation of multiple Krt genes, including Krt20, a biomarker of renal tubule injury. RNA-seq analysis highlights a cascade of temporal-specific gene expression patterns related to tubular injury/repair, fibrosis, and innate and adaptive immunity. Intersection of these data with human kidney transplant expression profiles identified overlapping gene expression signatures correlating with different stages of the murine IRI response. The comprehensive characterization of incomplete recovery after ischemic AKI provides a valuable resource for determining the underlying pathophysiology of human CKD.

Kidney injury enhances renal G-CSF expression and modulates granulopoiesis and human neutrophil CD177 in vivo

“…Long‐term follow‐up data after ischemia–reperfusion injury demonstrated elevated renal G‐CSF expression for at least 1 month after the event (Fig. d) .…”

“…(b, n = 3–5, Bonferroni after analysis of variance ( anova ), n.d. = not detectable) and UUO kidneys (c, n = 3–4, Bonferroni after anova ). (d) Long‐term regulation of renal G‐CSF gene expression was determined at the indicated time‐points after renal ischemia–reperfusion injury, after sham surgery and in control mice .…”

“…(a,b) G‐CSF ( Csf3 ) mRNA expression in human renal tubular epithelial HK2 cells (a) and human endothelial cells (HUVEC, b) after 24 h hypoxia (a,b, n = 3 for each cell type, t ‐tests). (c) Regulation of renal interleukin (IL)‐17A gene expression after renal ischemia–reperfusion injury in mice ( n = 3 per time‐point ). (d–f) G‐CSF ( Csf3 ) mRNA 6 and 24 h after stimulation with the indicated concentrations of recombinant human interleukin (IL)‐17A in HK2 [d,e, n = 3, Dunnett’s after analysis of variance ( anova )] and HUVEC after 24 h (f, n = 3, Dunnett’s after anova ).…”

Immune‐related gene expression profiles of hypothermia adipocytes: Implications for Bell's palsy

“…Over the past decade, RNA‐seq technology has emerged as a revolutionary and powerful tool for revealing the molecular expression profile and specific biological processes of disease development at the level of gene expression (Lee et al, ; Liu et al, ). Thus, obtaining a comprehensive molecular expression profile of adipocytes under acute cold exposure can help clarify the molecular mechanisms of adipocyte immune function that potentially impacts myelin.…”

MicroRNA-26a: An Emerging Regulator of Renal Biology and Disease

“…About 12.5% Americans suffer from chronic nephropathy. Acute kidney disease could directly cause renal failure and death [2]. On cellular scale, podocytes, mesangial cells (MCs), and T cells are often involved as dominant etiologic factors [3].…”