Post-Ischemic Renal Fibrosis Progression Is Halted by Delayed Contralateral Nephrectomy: The Involvement of Macrophage Activation.
Pál TodÉva Nóra BukoszaBeáta RókaTamás KaucsárAttila FinthaTibor KrenácsGábor SzénásiPéter HamarPublished in: International journal of molecular sciences (2020)
(1) Background: Successful treatment of acute kidney injury (AKI)-induced chronic kidney disease (CKD) is unresolved. We aimed to characterize the time-course of changes after contralateral nephrectomy (Nx) in a model of unilateral ischemic AKI-induced CKD with good translational utility. (2) Methods: Severe (30 min) left renal ischemia-reperfusion injury (IRI) or sham operation (S) was performed in male Naval Medical Research Institute (NMRI) mice followed by Nx or S one week later. Expression of proinflammatory, oxidative stress, injury and fibrotic markers was evaluated by RT-qPCR. (3) Results: Upon Nx, the injured kidney hardly functioned for three days, but it gradually regained function until day 14 to 21, as demonstrated by the plasma urea. Functional recovery led to a drastic reduction in inflammatory infiltration by macrophages and by decreases in macrophage chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α) mRNA and most injury markers. However, without Nx, a marked upregulation of proinflammatory (TNF-α, IL-6, MCP-1 and complement-3 (C3)); oxidative stress (nuclear factor erythroid 2-related factor 2, NRF2) and fibrosis (collagen-1a1 (Col1a1) and fibronectin-1 (FN1)) genes perpetuated, and the injured kidney became completely fibrotic. Contralateral Nx delayed the development of renal failure up to 20 weeks. (4) Conclusion: Our results suggest that macrophage activation is involved in postischemic renal fibrosis, and it is drastically suppressed by contralateral nephrectomy ameliorating progression.
Keyphrases
- oxidative stress
- ischemia reperfusion injury
- diabetic rats
- acute kidney injury
- chronic kidney disease
- nuclear factor
- robot assisted
- rheumatoid arthritis
- end stage renal disease
- adipose tissue
- poor prognosis
- cardiac surgery
- high glucose
- dna damage
- induced apoptosis
- toll like receptor
- drug induced
- editorial comment
- systemic sclerosis
- binding protein
- healthcare
- idiopathic pulmonary fibrosis
- genome wide
- minimally invasive
- type diabetes
- liver fibrosis
- early onset
- endothelial cells
- brain injury
- signaling pathway
- clinical trial
- gene expression
- inflammatory response
- small molecule
- gestational age
- randomized controlled trial
- study protocol
- preterm birth
- wild type
- endoplasmic reticulum stress
- blood brain barrier
- metabolic syndrome
- bioinformatics analysis