Abstract: SA-PO995
A New Role of Acute Phase Proteins: Local Production Is an Ancient, General Stress-Response System of Mammalian Cells
Session Information
- CKD: Pathobiology - II
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Author
- Hamar, Peter, Semmelweis Egyetem, Budapest, Budapest, Hungary
Background
The prevailing general view of acute-phase proteins (APPs) is that they are produced by the liver in response to the stress of the body as part of a systemic acute-phase response. We demonstrated a coordinated, local production of these proteins upon cell stress by the stressed cells.
Methods
Mouse left kidneys were subjected to 30 minutes ischemia. Contralateral right kidneys were removed on day 7. Furthermore, miR-193 transgenic renal fibrosis and bacterial endotoxin (LPS) induced acute renal injury and modulated electro-hyperthermia treatment of breast cancer were investigated. Fibrosis progression (blood urea, renal fibronectin, collagen and TGF-b expression) of the post-ischemic kidneys were assessed on day 8, 10, 14, 28 and 144. Next generation sequencing results were verified by nanostring and qPCR analysis. Protein level expression was profiled by mass spectrometry.
Results
Postischemic kidneys deteriorated resulting in a non-functional renal scar tissue within 28 days. This deterioration was delayed to 144 days by removal of the contralateral healthy kidney. The miR-193 transgene induced renal failure in 8 weeks and LPS induced AKI demonstrated by functional, morphologic and molecular data. Multiplex analysis of these models demonstrated a coordinated upregulation of several acute phase proteins on the mRNA and protein level in all 3 renal models. The similar APP response was demonstrated by us also in a breast cancer mouse model treated with hyperthermia.
Conclusion
The local, stress-induced APP production has been demonstrated in different tissues (kidney, breast cancer) and with different stressors (hypoxia, fibrosis and electromagnetic heat). Thus, this local acute-phase response (APR) seems to be a universal mechanism.
Papers presented: 10.3390/ijms23062972, 10.3390/ijms21155316, 10.3390/ijms21113825, 10.3390/ijms21010200
Funding
- Government Support – Non-U.S.