A Glimpse of the Mechanisms Related to Renal Fibrosis in Diabetic Nephropathy

Zeng, Lingfeng; Xiao, Ying; Sun, Lin

doi:10.1007/978-981-13-8871-2_4

Cited by 100 publications

(61 citation statements)

References 196 publications

(227 reference statements)

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“…The role of fibrosis in the progression of DN has also been recognized appearing to be critical for final progression of DN to kidney failure in diabetic Type 1 and 2 [19]. There is a positive correlation between the grade of fibrosis of the renal cortical interstitium and the serum creatinine concentration at the time of biopsy in patients with DN.…”

Section: Introductionmentioning

confidence: 99%

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Calle

Hotter

2020

IJMS

152

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Diabetic nephropathy (DN) is the leading cause of end-stage renal disease globally. The primary initiating mechanism in DN is hyperglycemia-induced vascular dysfunction, but its progression is due to different pathological mechanisms, including oxidative stress, inflammatory cells infiltration, inflammation and fibrosis. Macrophages (Mφ) accumulation in kidneys correlates strongly with serum creatinine, interstitial myofibroblast accumulation and interstitial fibrosis scores. However, whether or not Mφ polarization is involved in the progression of DN has not been adequately defined. The prevalence of the different phenotypes during the course of DN, the existence of hybrid phenotypes and the plasticity of these cells depending of the environment have led to inconclusive results. In the same sense the role of the different macrophage phenotype in fibrosis associated or not to DN warrants additional investigation into Mφ polarization and its role in fibrosis. Due to the association between fibrosis and the progressive decline of renal function in DN, and the role of the different phenotypes of Mφ in fibrosis, in this review we examine the role of macrophage phenotype control in DN and highlight the potential factors contributing to phenotype change and injury or repair in DN.

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Section: Introductionmentioning

confidence: 99%

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Calle

Hotter

2020

IJMS

152

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“…It is reported that every ischemic AKI insult diminishes the intrarenal total vascular surface area, subsequently followed or accompanied by endothelial-to-mesenchymal transdifferentiation (EndoMT) (O'Riordan et al, 2007;Zeisberg et al, 2008). EndoMT and epithelial-mesenchymal transition (EMT) was associated with increased collagen production and renal fibrosis (Cruz-Solbes & Youker, 2017;Zeng, Xiao & Sun, 2019). As an indicator of collagen metabolism, we speculated that the increase in urinary trans-4-hydroxy-L-proline after AKI may reflect mild renal fibrosis, which may be undetectable by normal assay and could be treated as an early warning of DN progression.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics window into the role of acute kidney injury after coronary artery bypass grafting in diabetic nephropathy progression

Wang

Yan

Zhou

et al. 2020

PeerJ

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Introduction Metabolomics has emerged as a valuable tool to discover novel biomarkers and study the pathophysiology of diabetic nephropathy (DN). However, the effect of postoperative acute kidney injury (AKI) on diabetes mellitus (DM) to chronic DN progression has not been evaluated from the perspective of metabolomics. Methods A group of type 2 diabetes mellitus (T2DM) inpatients, who underwent off-pump coronary artery bypass grafting (CABG), were enrolled in our study. According to whether postoperative AKI occurred, patients were grouped in either the AKI group (AKI, n = 44) or the non-AKI group (NAKI, n = 44). Urine samples were collected from these patients before and 24 h after operation. Six patients from the AKI group and six patients from the NAKI group were chosen as the pilot cohort for untargeted metabolomics analysis, with the goal of identifying postoperative AKI-related metabolites. To understand the possible role of these metabolites in the chronic development of renal injury among T2DM patients, trans-4-hydroxy-L-proline and azelaic acid were quantified by targeted metabolomics analysis among 38 NAKI patients, 38 AKI patients, 46 early DN patients (DN-micro group), and 34 overt DN patients (DN-macro group). Results Untargeted metabolomics screened 61 statistically distinguishable metabolites in postoperative urine samples, compared with preoperative urine samples. Via Venn diagram analysis, nine of 61 were postoperative AKI-related metabolites, including trans-4-hydroxy-L-proline, uridine triphosphate, p-aminobenzoate, caffeic acid, adrenochrome, δ-valerolactam, L-norleucine, 5′-deoxy-5′-(methylthio) adenosine, and azelaic acid. By targeted metabolomics analysis, the level of trans-4-hydroxy-L-proline increased gradually from the NAKI group to the AKI, DN-micro, and DN-macro groups. For azelaic acid, the highest level was found in the NAKI and DN-micro groups, followed by the DN-macro group. The AKI group exhibited the lowest level of azelaic acid. Conclusions The detection of urinary trans-4-hydroxy-L-proline after AKI could be treated as an early warning of chronic DN progression and might be linked to renal fibrosis. Urinary azelaic acid can be used to monitor renal function noninvasively in DM and DN patients. Our results identified markers of AKI on DM and the chronic progression of DN. In addition, the progression of DN was associated with AKI-like episodes occurring in DM.

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“…Furthermore, miR-21 was also increased under the condition of hyperglycemia and targeted to the expression of TSP-1 [61] which was linked to activation of TGF-β1/Smad7 signaling [62]. In contrast, other miR-NAs were reduced in diabetic conditions, such as miR-30c, miR-23, and miR-29 [63]. These miRNAs could significantly inhibit TGF-β1-induced EMT formation [64].…”

Section: Endoplasmic Reticulum (Er)mentioning

confidence: 99%

“…Second, miRNAs are involved in increasing the expression of TSP-1. For instance, deregulation of miR-320c, miR-21, and miR-192 which has an effect on TGF-β1 and TSP-1 attenuated the progression of DN [62,63,66]. Finally, suppression of ER stress could prevent the progression of fibrosis in DN [102], which might be associated with inhibiting the expression of TSP-1 [48].…”

Section: 1mentioning

confidence: 99%

Thrombospondin-1: A Key Protein That Induces Fibrosis in Diabetic Complications

Zhang

Chen

et al. 2020

Journal of Diabetes Research

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Fibrosis accompanies most common pathophysiological features of diabetes complications in different organs. It is characterized by an excessive accumulation of extracellular matrix (ECM) components, the response to which contributes to inevitable organ injury. The extracellular protein thrombospondin-1 (TSP-1), a kind of extracellular glycoprotein, is upregulated by the increased activity of some transcription factors and results in fibrosis by activating multiple pathways in diabetes. The results of studies from our team and other colleagues indicate that TSP-1 is associated with the pathological process leading to diabetic complications and is considered to be the most important factor in fibrosis. This review summarizes the molecular mechanism of increased TSP-1 induced by hyperglycemia and the role of TSP-1 in fibrosis during the development of diabetes complications.

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A Glimpse of the Mechanisms Related to Renal Fibrosis in Diabetic Nephropathy

Cited by 100 publications

References 196 publications

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy

Metabolomics window into the role of acute kidney injury after coronary artery bypass grafting in diabetic nephropathy progression

Thrombospondin-1: A Key Protein That Induces Fibrosis in Diabetic Complications

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