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Published on: April 26, 2019
Macrophage migration inhibitory factor is a possible candidate for the induction of microalbuminuria in diabetic
Tamaki Watanabe1, Naoko H Tomioka, Masaru Doshi
1Faculty of Pharma-Sciences, Teikyo University, Tokyo 173–8605, Japan.
Abstract:
Preventing the onset of microalbuminuria in diabetic nephropathy is a problem that needs urgent rectification. The use of a mouse model for diabetes is vital in this regard. For example, db/db mice exhibit defects in the leptin receptor Ob-Rb sub-type, while the ob/ob strain exhibits defects in the leptin ligand. These mouse strains demonstrate type 2 diabetes, either with or without microalbuminuria, respectively. The purpose of the present study was to use DNA microarray technology to screen for the gene responsible for the onset of diabetic microalbuminuria. Using Affymetrix Mouse Gene ST 1.0 arrays, microarray analysis was performed using total RNA from the kidneys of ob control, ob/ob, db/m, and db/db mice. Microarray and quantitative reverse transcription-polymerase chain reaction (RT-PCR) indicated that transcription of the macrophage migration inhibitory factor (MIF) gene was significantly enhanced in the kidneys of db/db mice. Western blotting showed that levels of MIF protein was enhanced in the kidneys of both diabetic db/db and ob/ob mice. On the other hand, elevation of urinary MIF excretion detected by enzyme-linked immunosorbent assay (ELISA) was only in db/db mice and preceded the onset of microalbuminuria. Immunofluorescence studies revealed that MIF was expressed in mouse kidney glomeruli. While MIF expression was enhanced in the diabetic kidneys of both mouse strains, the elevated secretion from db/db mouse kidneys may be responsible for initiating the onset of microalbuminuria in diabetic nephropathy.
Insights
Diabetic nephropathy and microalbuminuria prevention is critical. Macrophage migration inhibitory factor (MIF) gene expression increased in db/db mouse kidneys, preceding microalbuminuria onset, suggesting its role in diabetic kidney disease.
Area of Science:
- Nephrology
- Endocrinology
- Genetics
Background:
- Diabetic nephropathy is a serious complication of diabetes, often leading to microalbuminuria.
- Mouse models like db/db and ob/ob are crucial for studying type 2 diabetes and its renal manifestations.
- Identifying genes involved in microalbuminuria onset is vital for developing preventative strategies.
Purpose of the Study:
- To screen for genes responsible for the onset of diabetic microalbuminuria using DNA microarray technology.
- To investigate the role of macrophage migration inhibitory factor (MIF) in diabetic nephropathy.
- To compare gene expression profiles in different mouse models of diabetes.
Main Methods:
- Utilized DNA microarray analysis (Affymetrix Mouse Gene ST 1.0) on kidney RNA from ob control, ob/ob, db/m, and db/db mice.
- Performed quantitative reverse transcription-polymerase chain reaction (RT-PCR) to validate microarray findings.
- Employed Western blotting to assess protein levels and enzyme-linked immunosorbent assay (ELISA) for urinary MIF excretion.
Main Results:
- Macrophage migration inhibitory factor (MIF) gene transcription was significantly enhanced in db/db mouse kidneys.
- MIF protein levels were elevated in the kidneys of both db/db and ob/ob diabetic mice.
- Elevated urinary MIF excretion, detected by ELISA, was specific to db/db mice and preceded microalbuminuria onset.
Conclusions:
- Enhanced MIF gene expression and protein levels are associated with diabetic nephropathy in mice.
- Elevated urinary MIF excretion in db/db mice suggests a key role in initiating microalbuminuria.
- MIF, expressed in kidney glomeruli, may be a critical factor in the development of diabetic microalbuminuria.
