23 Additionally, by immunohistochemical tactics a broad spread expression of Epac1 and Epac2 in almost each of the compartments of your kidney is reported. 30 In see of such relatively controversial details, initial Epac1 gene expression was investigated by using greater than a single procedure. Northern blot analyses exposed Epac1 expression in the heart and kidney, and no expression in other organs.These findings are at variance with prior scientific studies, and conceivably this may well be re lated to the methodology utilized. However, a readily detectable expression within the kidney, albeit not as heavy as inside the cardiac musculature, would suggest a plausible purpose of Epac1 in the pathophysiology of the kidney as well. In pursuance with this notion in situ hybridization research have been carried out to assess the Epac1 gene ex pression in a variety of compartments with the kidney.
The ex pression was mostly confined to your cortical tubules and to a lesser degree in the medullary tubules,suggesting they might have some position while in the patho physiology of renal tubules. Indeed, Epac1 has become proven to modulate Na H exchanger 3 ex pressed during the brush border membrane of proximal tu bules, and also to regulate UT A1 phosphorylation to accentuate transport of urea in inner medullary collecting ducts. our site 31,32 These find more info studies propose that Epac1 is relevant on the pathophysiology with the tubules. In light from the fact that its downstream target, Rap1b, is co expressed and it is up regulated by hyperglycemia,20 we proceeded to investigate the Epac1 expression in diabetic state. A multitude of approaches, including in situ hybridization, im munohistochemistry, and Northern and Western blot analyses, uncovered a rise inside the Epac1 expression in proportion to your degree of hyperglycemia, especially during the tubular compartment,hence suggesting its relevance in the pathogenesis of diabetic nephropathy.
Within this regard, besides Epac1s downstream target, Rap1b, other tiny GTPase, like Rho and Ras, have also been shown for being up regulated in renal cells sub jected to substantial glucose ambience,33 36 which additional strengthens the impetus to carry out the research and elu cidate the mechanisms by which Epac1 exerts its influ ence in the pathogenesis of diabetic nephropathy. In vitro culture approaches have been utilised to delineate the mechanisms pertinent to tubular pathology in diabetic ne phropathy. Initial, numerous cell lines had been made use of and expres sion of Epac1 was investigated by RT PCR analyses.