Molecular Mechanisms of Kidney Injury and Repair in Arterial Hypertension

Abstract

The global burden of chronic kidney disease is rising. The etiologies, heterogeneous, and arterial hypertension, are key factors contributing to the development and progression of chronic kidney disease. Arterial hypertension is induced and maintained by a complex network of systemic signaling pathways, such as the hormonal axis of the renin-angiotensin-aldosterone system, hemodynamic alterations affecting blood flow, oxygen supply, and the immune system. This review summarizes the clinical and histopathological features of hypertensive kidney injury and focusses on the interplay of distinct systemic signaling pathways, which drive hypertensive kidney injury in distinct cell types of the kidney. There are several parallels between hypertension-induced molecular signaling cascades in the renal epithelial, endothelial, interstitial, and immune cells. Angiotensin II signaling via the AT1R, hypoxia induced HIFα activation and mechanotransduction are closely interacting and further triggering the adaptions of metabolism, cytoskeletal rearrangement, and profibrotic TGF signaling. The interplay of these, and other cellular pathways, is crucial to balancing the injury and repair of the kidneys and determines the progression of hypertensive kidney disease.

Kidney Inflammation, Injury and Regeneration

“…This Special Issue covers research articles that investigated the molecular mechanisms of inflammation [1][2][3] and injury [4,5] during different renal pathologies and renal regeneration [6], diagnostics using new biomarkers [7][8][9], and the effects of different stimuli like medication or bacterial components on isolated renal cells or in vivo models [10][11][12], all of which were summarized in a very simplified manner. Furthermore, this Special Issue contains important reviews that dealt with the current knowledge of cell death and regeneration [13,14], inflammation [15][16][17][18], and the molecular mechanisms of kidney diseases [19][20][21][22]. In addition, the potential of cell-based therapy approaches that use mesenchymal stromal/stem cells (MSCs) or their derivates is summarized [23][24][25].…”

“…Priante and co-workers reviewed the different modalities of apoptosis, necrosis, and regulated necrosis in kidney injuries in order to find evidence for the role of cell death, which may pave the way for new therapeutic opportunities [14]. Others discussed the molecular basis of injury and repair in distinct cell types of the kidney during arterial hypertension [21]. In this context, the main mechanisms of kidney regeneration, while focusing on epithelial cell dedifferentiation and the activation of progenitor cells with special attention on the potential niches of kidney progenitor cells, were also lighted [13].…”

Research progress in acute hypertensive renal injury by “in vivo cryotechnique”

“…Besides the characteristic vascular adaptations and glomerular pathology, kidney histology of hypertensive nephrosclerosis may also show trans-differentiation and apoptosis of tubular cells, increased peritubular fibrosis, fibroblasts proliferation, and increased interstitial inflammation. [8]…”

Hesperidin inhibits L‐NAME‐induced vascular and renal alterations in rats by suppressing the renin–angiotensin system, transforming growth factor‐β1, and oxidative stress

“…Elevated arterial blood pressure in association with vascular endothelial dysfunction and structural changes is referred to as vascular remodelling 1 . Additionally, long‐term hypertension causes increased intraglomerular pressure, glomerular damage, and impaired glomerular filtration and leads to the progression of chronic renal diseases 2 . Chronic administration of N ω ‐nitro‐l‐arginine methyl ester hydrochloride (L‐NAME), a nitric oxide synthesis inhibitor, has been demonstrated to induce hypertension together with vascular and renal alterations.…”