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Diabetic nephropathy (DN) is one of the major leading cause of kidney failure. To identify the progression of chronic kidney disease (CKD), renal function/fibrosis is playing a crucial role. Unfortunately, lack of sensitivities/specificities of available clinical biomarkers are key major issues for practical healthcare applications to identify the renal functions/fibrosis in the early stage of DN. Thus, there is an emerging approach such as therapeutic or diagnostic are highly desired to conquer the CKD at earlier stages. Herein, we applied and examined the application of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and diffusion weighted imaging (DWI) to identify the progression of fibrosis between wild type (WT) and miR29a transgenic (Tg) mice during streptozotocin (STZ)-induced diabetes. Further, we also validate the potential renoprotective role of miR29a to maintain the renal perfusion, volume, and function. In addition, Ktrans values of DCE-MRI and apparent diffusion coefficient (ADC) of DWI could significantly reflect the level of fibrosis between WT and Tg mice at identical conditions. As a result, we strongly believed that the present non-invasive MR imaging platforms have potential to serveas an important tool in research and clinical imaging for renal fibrosis in diabetes, and that microenvironmental changes could be identified by MR imaging acquisition prior to histological biopsy and diabetic podocyte dysfunction. [ABSTRACT FROM AUTHOR]

Intensive fibrosis in the glomerular microenvironment is a prominent feature of diabetic nephropathy. Cannabinoid receptor 1 (CB1R) reportedly mediates diabetes-induced renal injury. However, studies on the molecular events underlying CB1R promotion of renal dysfunction are limited. This study is undertaken to investigate whether CB1R signaling via Ras or PPARγ pathway regulates mesangial fibrosis in diabetic kidneys. In streptozotocin-induced diabetic rats, hyperglycemia induced glomerular hypertrophy and fibrosis in association with increased IL-1β, fibronectin, and CB1R expressions and reduced PPARγ2 signaling. CB1R transgenic mice gained kidney weight, and renal glomeruli strongly displayed IL-1β and fibrotic matrices. Disruption of CB1R by antisense oligonucleotides or inverse agonist AM251 restored PPARγ2 signaling and reduced the promotional effects of hyperglycemia on the expression of fibrogenic transcription factor c-Jun, inflammation regulator SOCS3, proinflammatory cytokines, and accumulation of fibrotic matrix. PPARγ agonist rosiglitazone reduced the hyperglycemia-mediated enhancement of CB1R signaling, inflammation, and glomerular fibrosis in diabetic animals. In vitro, CB1R antagonism restored PPARγ2 action and reduced the promotional effects of high glucose on Ras, ERK, c-Jun, SOCS3 signaling, IL-1β, and fibronectin expression in renal mesangial cells. Activation of PPARγ2 reduced the high glucose-induced CB1R expression in mesangial cells. Taken together, CB1R signaling contributes to the hyperglycemia disturbance of PPARγ2 signaling and increases inflammatory cytokine secretion and fibrotic matrix deposition in renal glomeruli. CB1R mediates the hyperglycemia-induced inflammation and fibrosis in mesangial cells by regulating Ras, ERK, and PPARγ2 signaling. CB1R blockade has a therapeutic potential to reduce the deleterious actions of hyperglycemia on renal glomerular integrity. Key message: [ABSTRACT FROM AUTHOR]