Podocyte injury of diabetic nephropathy: Novel mechanism discovery and therapeutic prospects

Li, Xiandeng; Zhang, Ying; Xing, Xiaodong; Li, Mi; Liu, Yan; Xu, Ajing; Zhang, Jian

doi:10.1016/j.biopha.2023.115670

Cited by 17 publications

(6 citation statements)

References 166 publications

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“…It is known that typical lesions of diabetic nephropathy include glomerular hyperfiltration and podocyte injury. Among the mechanisms of podocyte injury are lipotoxicity, oxidative stress, mitochondrial damage, and autophagy ( Li et al, 2023b ; Nagata, 2016 ). In fact, the molecular mechanism of DN is complex and many pathways are involved in DN development and progression in a hyperglycemic environment including polyol, hexosamine, PKC, and AGE pathways.…”

Section: Discussionmentioning

confidence: 99%

A retrospective cohort study of clinical characteristics and outcomes of type 2 diabetic patients with kidney disease

He,

Deng,

Tian

et al. 2024

PeerJ

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Background Type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD) poses a serious health threat and becomes a new challenge. T2DM patients with CKD fall into three categories, diabetic nephropathy (DN), non-diabetic kidney disease (NDKD), and diabetic nephropathy plus non-diabetic kidney disease (DN + NDKD), according to kidney biopsy. The purpose of our study was to compare the clinical characteristics and kidney outcomes of DN, NDKD, and DN + NDKD patients. Methods Data on clinical characteristics, pathological findings, and prognosis were collected from June 2016 to July 2022 in patients with previously diagnosed T2DM and confirmed DN and or NDKD by kidney biopsy at Tongji Hospital in Wuhan, China. The endpoint was defined as kidney transplantation, dialysis, or a twofold increase in serum creatinine. Results In our 6-year retrospective cohort research, a total of 268 diabetic patients were admitted and categorized into three groups by kidney biopsy. The 268 patients were assigned to DN (n = 74), NDKD (n = 109), and DN + NDKD (n = 85) groups. The most frequent NDKD was membranous nephropathy (MN) (n = 45,41.28%). Hypertensive nephropathy was the most common subtype in the DN+NDKD group (n = 34,40%). A total of 34 patients (12.7%) reached the endpoint. The difference between the Kaplan-Meier survival curves of the DN, NDKD, and DN + NDKD groups was significant (p < 0.05). Multifactorial analysis showed that increased SBP [HR (95% CI): 1.018(1.002–1.035), p = 0.025], lower Hb [HR(95% CI): 0.979(0.961–0.997), p = 0.023], higher glycosylated hemoglobin [HR(95% CI): 1.338(1.080–1.658), p = 0.008] and reduced serum ALB [HR(95% CI): 0.952(0.910–0.996), p = 0.032] were risk factors for outcomes in the T2DM patients with CKD. Conclusions This research based on a Chinese cohort demonstrated that the risk of endpoint events differed among DN, NDKD, and DN+NDKD patients. In T2DM patients with CKD, DN patients displayed worse kidney prognosis than those with NDKD or DN + NDKD. Increased SBP, higher glycosylated hemoglobin, lower Hb, and decreased serum ALB may be correlated with adverse kidney outcomes in T2DM patients.

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Section: Discussionmentioning

confidence: 99%

A retrospective cohort study of clinical characteristics and outcomes of type 2 diabetic patients with kidney disease

He,

Deng,

Tian

et al. 2024

PeerJ

View full text Add to dashboard Cite

show abstract

“…73 A growing body of research has demonstrated a tight relationship between podocyte injury and the onset and progression of DKD. 74 Pathologic changes such as decreased podocyte density and structural or functional abnormalities of podocytes after podocyte injury can lead to albuminuria. 75 It is now known that DKDrelated lncRNAs influence podocyte injury caused by DKD.…”

Section: Dkd-related Lncrnas Promote Podocyte Injurymentioning

confidence: 99%

The role of long non‐coding RNAs in the development of diabetic kidney disease and the involved clinical application

Hou,

2024

Diabetes Metabolism Res

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Diabetic kidney disease (DKD), one of the common microvascular complications of diabetes, is increasing in prevalence worldwide and can lead to End‐stage renal disease. However, there are still gaps in our understanding of the pathophysiology of DKD, and both current clinical diagnostic methods and treatment strategies have drawbacks. According to recent research, long non‐coding RNAs (lncRNAs) are intimately linked to the developmental process of DKD and could be viable targets for clinical diagnostic decisions and therapeutic interventions. Here, we review recent insights gained into lncRNAs in pathological changes of DKD such as mesangial expansion, podocyte injury, renal tubular injury, and interstitial fibrosis. We also discuss the clinical applications of DKD‐associated lncRNAs as diagnostic biomarkers and therapeutic targets, as well as their limitations and challenges, to provide new methods for the prevention, diagnosis, and treatment of DKD.

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“…Podocytes are epithelial cells in the dirty layer of the renal capsule that attach to the outer glomerular basement membrane and, together with vascular endothelial cells and the glomerular basement membrane, constitute the glomerular filtration barrier function ( Garg, 2018 ). Upon the relentless influence of hyperglycemia, podocytes are subject to a series of detrimental changes including hypertrophy, apoptosis, epithelial-to-mesenchymal transition (EMT), and autophagy ( Li et al, 2023 ). These transformations are manifested by cytoskeletal remodeling, decline in slit diaphragms, depletion of foot-processes, and a reduction in their own number ( Thomas et al, 2015 ; Garg, 2018 ).…”

Section: Therapeutic Effects and Mechanisms Of Salidroside In Renal D...mentioning

confidence: 99%

Pharmacological functions of salidroside in renal diseases: facts and perspectives

Liu,

Chen,

Zeng

et al. 2024

Front. Pharmacol.

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Rhodiola rosea is a valuable functional medicinal plant widely utilized in China and other Asian countries for its anti-fatigue, anti-aging, and altitude sickness prevention properties. Salidroside, a most active constituent derived from Rhodiola rosea, exhibits potent antioxidative, hypoxia-resistant, anti-inflammatory, anticancer, and anti-aging effects that have garnered significant attention. The appreciation of the pharmacological role of salidroside has burgeoned over the last decade, making it a beneficial option for the prevention and treatment of multiple diseases, including atherosclerosis, Alzheimer’s disease, Parkinson’s disease, cardiovascular disease, and more. With its anti-aging and renoprotective effects, in parallel with the inhibition of oxidative stress and inflammation, salidroside holds promise as a potential therapeutic agent for kidney damage. This article provides an overview of the microinflammatory state in kidney disease and discuss the current therapeutic strategies, with a particular focus on highlighting the recent advancements in utilizing salidroside for renal disease. The potential mechanisms of action of salidroside are primarily associated with the regulation of gene and protein expression in glomerular endothelial cells, podocytes, renal tubule cells, renal mesangial cells and renal cell carcinoma cell, including TNF-α, TGF-β, IL-1β, IL-17A, IL-6, MCP-1, Bcl-2, VEGF, ECM protein, caspase-3, HIF-1α, BIM, as well as the modulation of AMPK/SIRT1, Nrf2/HO-1, Sirt1/PGC-1α, ROS/Src/Cav-1, Akt/GSK-3β, TXNIP-NLRP3, ERK1/2, TGF-β1/Smad2/3, PI3K/Akt, Wnt1/Wnt3a β-catenin, TLR4/NF-κB, MAPK, JAK2/STAT3, SIRT1/Nrf2 pathways. To the best of our knowledge, this review is the first to comprehensively cover the protective effects of salidroside on diverse renal diseases, and suggests that salidroside has great potential to be developed as a drug for the prevention and treatment of metabolic syndrome, cardiovascular and cerebrovascular diseases and renal complications.

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Podocyte injury of diabetic nephropathy: Novel mechanism discovery and therapeutic prospects

Cited by 17 publications

References 166 publications

A retrospective cohort study of clinical characteristics and outcomes of type 2 diabetic patients with kidney disease

A retrospective cohort study of clinical characteristics and outcomes of type 2 diabetic patients with kidney disease

The role of long non‐coding RNAs in the development of diabetic kidney disease and the involved clinical application

Pharmacological functions of salidroside in renal diseases: facts and perspectives

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