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The discovery of putative urinary marker for detection of type 1 diabetic nephropathy by integrative mining of public miRNA databases
Transcript of The discovery of putative urinary marker for detection of type 1 diabetic nephropathy by integrative mining of public miRNA databases
The discovery of putative urine marker for detection of Type 1 diabetic nephropathy by integrative mining of public miRNA databases
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.
Aim of work
Patients and methods
Our presentation consists of :
Mechanisms of Diabetic nephropathy
What is urinary exosome?
It is 40-100 nm vesicles.
Containing protein, mRNA, miRNA.
Can be isolated for proteomic analysis and RNA profiling.
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.
for DN rather than a
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.
Non-albuminuric Type 1 diabetic patients
Micro-albuminuric Type 1 diabetic patients
Macro-albuminuric Type 1 diabetic patients
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.
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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
Progressive increase in
urine albumin excretion
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
diabetes ass. hyperglycemia
Activation of secretion of TGF ß
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.
is defined as an ACR between 30-300 mg/g.
is defined as an ACR > 300 mg/g.
2 of 3 samples
should fall within the microalbuminuric or macroalbuminuric range to confirm classification.