Abstract
Accumulating evidence indicates that epithelial-to-mesenchymal transition (EMT), originally described as a key process for organ development and metastasis budding in cancer, plays a key role in the development of renal fibrosis in several diseases, including hypertensive nephroangiosclerosis. We herein reviewed the concept of EMT and its role in renal diseases, with particular focus on hypertensive kidney disease, the second leading cause of end-stage renal disease after diabetes mellitus. After discussing the pathophysiology of hypertensive nephropathy, the ‘classic’ view of hypertensive nephrosclerosis entailing hyalinization, and sclerosis of interlobular and afferent arterioles, we examined the changes occurring in the glomerulus and tubulo-interstitium and the studies that investigated the role of EMT and its molecular mechanisms in hypertensive kidney disease. Finally, we examined the reasons why some studies failed to provide solid evidence for renal EMT in hypertension.
Highlights
More than 20 million people have chronic kidney disease (CKD) in the US, with 3% of them developing end-stage renal disease (ESRD), which accounts for 7% of Medicare expenditures
Depending on the underlying pathophysiology and/or severity of HT, multiple mechanisms can concur to induce tubular-interstitial fibrosis (TIF), among which is epithelial-to-mesenchymal transition (EMT), a process originally described in organ development and metastasis budding in cancer, and later observed in several diseases [10,11]
Using a transgenic renin-dependent model of severe HT and cardiovascular and renal damage created with insertion of the mouse renin gene into the rat genome, the TG(mRen2)27 rat, we found that a blockade of the angiotensin II (Ang II) type 1 (AT1) receptor with irbesartan prevented TIF, supporting a fibrogenic role of Ang II [8]
Summary
More than 20 million people have chronic kidney disease (CKD) in the US, with 3% of them developing end-stage renal disease (ESRD) (https://www.usrds.org/adr.aspx), which accounts for 7% of Medicare expenditures. The medical spending is held to be much greater, because ESRD patients are at high risk of cardio- and cerebrovascular vascular disease, which is projected to rise even more, owing to population ageing in the decades [2]. Even though classically described as nephroangiosclerosis and hyalinosis of the glomerular tuft [6,7], hypertensive nephropathy has been more recently found to involve the glomerular and vascular compartments, and the interstitium, because of the development of tubular-interstitial fibrosis (TIF) and, ESRD [8,9]. Depending on the underlying pathophysiology and/or severity of HT, multiple mechanisms can concur to induce TIF, among which is epithelial-to-mesenchymal transition (EMT), a process originally described in organ development and metastasis budding in cancer, and later observed in several diseases [10,11]. We shall focus on the EMT process and its involvement in hypertensive nephropathy by exploiting a methodology to systematically review the English-written literature by means of a PICO (Patient or Problem, Intervention, Comparison, Outcome) search strategy (Table 1) with selection of the articles based on their relevance, rigorousness of study design and methodology, and appropriateness of data interpretation
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