In this review, we briefly summarize underlying mechanisms of autophagy dysregulation in DKD, including AMP-activated protein kinase (AMPK), the mechanistic target of rapamycin (mTOR), and the sirtuin (Sirt) pathways, and we particularly concentrate on the current status of Chinese herbal medicine treating DKD by regulating autophagy.
The goal of this study was to test the hypothesis that elevation of systemic ADMA levels by knocking out DDAH1 would exacerbate functional and structural glomerular abnormalities in a murine model of diabetic nephropathy.
Furthermore, miR-96-5p was downregulated in DKD mice, and this downregulation attenuated the repression of FN1(fibronectin, FN) and led to its upregulation.
However, epigenome and transcriptome effects of MIC-1 in kidney mesangial cells challenged with high glucose (HG), a pre-condition for diabetic nephropathy (DN) remain unknown.
However, epigenome and transcriptome effects of MIC-1 in kidney mesangial cells challenged with high glucose (HG), a pre-condition for diabetic nephropathy (DN) remain unknown.
It is possible that novel markers portraying the pathophysiological underpinning processes may be useful.<b>Aim:</b> To investigate the associations between 80 circulating proteins, measured by a proximity extension assay, and prevalent DKD and major adverse cardiovascular events (MACE) in type 2 diabetes.<b>Methods:</b> We randomly divided individuals with type 2 diabetes from three cohorts into a two-thirds discovery and one-third replication set (total <i>n</i> = 813, of whom 231 had DKD defined by estimated glomerular filtration rate <60 mg/mL/1.73 m<sup>2</sup> and/or urinary albumin-creatinine ratio ≥3 g/mol).
Proteins associated with DKD were also assessed as predictors for incident major adverse cardiovascular events (MACE) in persons with DKD at baseline.<b>Results:</b> Four proteins were positively associated with DKD in models adjusted for age, sex, cardiovascular risk factors, glucose control, and diabetes medication: kidney injury molecule-1 (KIM-1, odds ratio [OR] per standard deviation increment, 1.65, 95% confidence interval [CI] 1.27-2.14); growth differentiation factor 15 (GDF-15, OR 1.40, 95% CI 1.16-1.69); myoglobin (OR 1.57, 95% CI 1.30-1.91), and matrix metalloproteinase 10 (MMP-10, OR 1.43, 95% CI 1.17-1.74).
In patients with DKD, GDF-15 was significantly associated with increased risk of MACE after adjustments for baseline age, sex, microalbuminuria, and kidney function and (59 MACE events during 7 years follow-up, hazard ratio per standard deviation increase 1.43 [95% CI 1.03-1.98]) but not after further adjustments for cardiovascular risk factors.<b>Conclusion:</b> Our proteomics approach confirms and extends previous associations of higher circulating levels of GDF-15 with both micro- and macrovascular disease in patients with type 2 diabetes.
Proteins associated with DKD were also assessed as predictors for incident major adverse cardiovascular events (MACE) in persons with DKD at baseline.<b>Results:</b> Four proteins were positively associated with DKD in models adjusted for age, sex, cardiovascular risk factors, glucose control, and diabetes medication: kidney injury molecule-1 (KIM-1, odds ratio [OR] per standard deviation increment, 1.65, 95% confidence interval [CI] 1.27-2.14); growth differentiation factor 15 (GDF-15, OR 1.40, 95% CI 1.16-1.69); myoglobin (OR 1.57, 95% CI 1.30-1.91), and matrix metalloproteinase 10 (MMP-10, OR 1.43, 95% CI 1.17-1.74).
Proteins associated with DKD were also assessed as predictors for incident major adverse cardiovascular events (MACE) in persons with DKD at baseline.<b>Results:</b> Four proteins were positively associated with DKD in models adjusted for age, sex, cardiovascular risk factors, glucose control, and diabetes medication: kidney injury molecule-1 (KIM-1, odds ratio [OR] per standard deviation increment, 1.65, 95% confidence interval [CI] 1.27-2.14); growth differentiation factor 15 (GDF-15, OR 1.40, 95% CI 1.16-1.69); myoglobin (OR 1.57, 95% CI 1.30-1.91), and matrix metalloproteinase 10 (MMP-10, OR 1.43, 95% CI 1.17-1.74).
In conclusion, our study demonstrated the contribution of the PRR to the reduction of mitochondrial biogenesis and function in diabetic kidney disease via decreasing AMPK/SIRT-1/ PGC-1α signaling pathway.