Fibrosis and Inflammation Models
Inflammation is part of the body’s defence mechanism, a response to an irritant such as a pathogen or chemical substance. Inflammation initiates tissue repair. Fibrosis on the other hand is a process of pathological wound healing. Fibrotic scarring in central organs such as the liver or kidney due to excessive accumulation of extracellular matrix (ECM) leads to distortion of the tissue architecture and ultimately loss of organ function. Severe fibrosis is estimated to account for 45% of deaths in the developed world and treatment options are limited.
Here at Sygnature (formerly under the name RenaSci), we have established a range of in vivo and ex vivo pharmacology models, which enable careful assessment of drug candidates.
Examples of our validated and advanced Inflammation models include:
| Therapeutic Indication | Models | Characteristics |
| Kidney Disease | Adriamycin Model (mouse) | Focal segmental glomerulosclerosis (FSGS), moderate-severe fibrosis |
| Anti-GBM Model (mouse and rat) | Nephrotoxic nephritis (NTS), inflammation | |
| STZ/HFD Model (mouse and rat) | Diabetic nephropathy | |
| ZDF Model (rat) | Diabetic nephropathy, inflammation, fibrosis | |
| Liver Disease:
NASH and fibrosis |
Choline deficient (CD) model (mouse) | Moderate fibrosis with NASH, non-obese without metabolic disease |
| H-FFC model (mouse) | Moderate fibrosis with NASH, hyperglycaemia and overweight | |
| H-FFC ob/ob model (mouse) | Moderate fibrosis with NASH, hyperglycaemia, insulin resistance, dyslipidaemia and obesity | |
| H-FFC CCl4 model (mouse) | Severe fibrosis with severe NASH, non-obese without metabolic disease |
The study design elements for assessing novel drug potential include:
Kidney function and pathology readouts:
- Kidney histopathology: glomerulosclerosis, tubulointerstitial inflammation, glomerular fibrosis, tubulointerstitial fibrosis and more
- Plasma biomarkers: urea, creatinine, cystatin C, glucose, insulin, HbA1c, glucose tolerance and more
- Urinary biomarkers: ACR, PCR, creatinine clearance and inulin clearance, urinary glucose excretion, TIM-1, NGAL and more
Liver function and pathology readouts:
- Liver histopathology: steatosis, hepatic ballooning, lobular inflammation, NAFLD activity scoring (NAS), fibrosis, F4/80, α-SMA and more
- Liver biochemistry: hydroxyproline, triglyceride, cholesterol, NEFA content and more
- Plasma biomarkers: TIMP-1, PIIINP, Hyaluronic acid, ELF test, ALT, AST, bilirubin and more