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The discovery of putative urinary marker for detection of type 1 diabetic nephropathy by integrative mining of public miRNA databases

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rowaida reda

on 10 May 2014

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Transcript of The discovery of putative urinary marker for detection of type 1 diabetic nephropathy by integrative mining of public miRNA databases

Diabetic Nephropathy
The discovery of putative urine marker for detection of Type 1 diabetic nephropathy by integrative mining of public miRNA databases


Exosomes
Aim of work
To select miRNA relevant to type 1 diabetic nephropathy from the databases and to evaluate its usefulness as a urine molecular marker for early diabetic nephropathy detection.
Definition


Exosomal miRNA

Diabetic Nephropathy
Definition.

Molecular mechanisms.

Diagnosis.




Aim of work
Patients and methods
Our presentation consists of :
Mechanisms of Diabetic nephropathy
Urinary exosomes
What is urinary exosome?

It is 40-100 nm vesicles.
Containing protein, mRNA, miRNA.
Can be isolated for proteomic analysis and RNA profiling.


Exosomal miRNA
Exosomes are normally secreted in urine.
Exosomes contain miRNA.
So by isolating exosomes we can perform miRNA profiling
To evaluate expression of miRNA in patients with diabetic nephropathy.


Definition
Diagnosis
Microalbuminuria
But.....
Is a
marker
for DN rather than a
predictor
for its progression.
There is, thus, an increasing quest to find novel biomarkers.

Why early detection of DN ?
To identify and treat individuals at high risk.

To reduce the incidence of end stage renal disease and death.

Bioinformatic analysis
Experimental work
Patients
Group 1
Non-albuminuric Type 1 diabetic patients
Group 2
Micro-albuminuric Type 1 diabetic patients
Group 3
Macro-albuminuric Type 1 diabetic patients
Group 4
Healthy volunteers
References
M. Lucrecia Alvarez, Johanna K. DiStefano (2013) “The role of non coding RNAs in Diabetic nephropathy” diabetes research and clinical practice 99( 2013 ) 1– 11.
Declèves AE, Sharma K (2010). New pharmacological treatments for improving renal outcomes in diabetes. Nat Rev Nephrol 6: 371–380.
Lee HS (2013) Pathogenic Role of TGF- β in Diabetic Nephropathy. J Diabetes Metab S9: 008. doi:10.4172/2155-6156.S9-008.
Tolouian R, Hernandez GT(2013). Prediction of Diabetic Nephropathy:The need for a sweet biomarker. J Nephropathology. 2013; 2(1): 4-5.DOI: 10.5812/nephropathol.8966

Villeneuve, L.M.; Natarajan, R (2010). The role of epigenetics in the pathology of diabetic complications. Am. J. Physiol. Ren. Physiol. 2010, 299, F14–F25.
Ichimi T., Hideki Enokida1, Yasushi Okuno, Ryo Kunimoto, Takeshi Chiyomaru, Ken Kawamoto, Kazuya Kawahara, Kazuki Toki1, Kazumori Kawakami, Kenryu Nishiyama, Gozoh Tsujimoto, Masayuki Nakagawa and Naohiko Seki (2009): Identification of novel microRNA targets based on microRNA signatures in bladder cancer. Int. J. Cancer: 000, 000–000 (2009)
Barutta F, Tricarico M, Corbelli A, Annaratone L, Pinach S, et al. (2013) Urinary Exosomal MicroRNAs in Incipient Diabetic Nephropathy. PLoSONE 8(11): e73798. doi:10.1371/journal.pone.0073798

Exosomes
Progressive increase in
urine albumin excretion
accompanied by
declining GFR
&
rising BL pr
.
It is a major microvascular complication of diabetes.
It can manifest despite tight glycemic control and various therapeutic intervention.
The leading cause of ESRD
( 30-40%)
.
diabetes ass. hyperglycemia
Activation of secretion of TGF ß
miRNA
DNA methylation
changes in chromatin remodeling
Enhanced vascular complications...eg: Diabetic glomerulosclerosis
Patients and methods
Persistent elevation of ACR (Albumin Creatinine Ratio) for 3 successive sampling in 6 months duration.
Microalbuminuria
is defined as an ACR between 30-300 mg/g.
Macroalbuminuria
is defined as an ACR > 300 mg/g.
2 of 3 samples
should fall within the microalbuminuric or macroalbuminuric range to confirm classification.
Full transcript