ACSL5 promotes lipid deposition and lipoapoptosis in proximal tubular epithelial cells of diabetic kidney disease.

Background: Lipoapoptosis in Proximal tubular epithelial cells (PTCs) are substantial in the etiology of diabetic kidney disease (DKD), yet the underlying mechanisms warrant further investigation. Acyl-CoA synthetase long-chain family member 5 (ACSL5) facilitates the formation of acyl-CoA, however, the precise role of ACSL5 in lipoapoptosis of PTCs in DKD remains inconclusive.

Methods: Transcriptomic data analysis identified the hub gene Acsl5 associated with lipid metabolism in DKD.

PACS-2 deficiency aggravates tubular injury in diabetic kidney disease by inhibiting ER-phagy.

Autophagy of endoplasmic reticulum (ER-phagy) selectively removes damaged ER through autophagy-lysosome pathway, acting as an adaptive mechanism to alleviate ER stress and restore ER homeostasis. However, the role and precise mechanism of ER-phagy in tubular injury of diabetic kidney disease (DKD) remain obscure. In the present study, we demonstrated that ER-phagy of renal tubular cells was severely impaired in streptozocin (STZ)-induced diabetic mice, with a decreased expression of phosphofurin acidic cluster sorting protein 2 (PACS-2), a membrane trafficking protein which was involved in autophagy, and a reduction of family with sequence similarity 134 member B (FAM134B), one ER-phagy receptor.

DsbA-L interacting with catalase in peroxisome improves tubular oxidative damage in diabetic nephropathy.

Peroxisomes are metabolically active organelles that are known for exerting oxidative metabolism, but the precise mechanism remains unclear in diabetic nephropathy (DN). Here, we used proteomics to uncover a correlation between the antioxidant protein disulfide-bond A oxidoreductase-like protein (DsbA-L) and peroxisomal function. In vivo, renal tubular injury, oxidative stress, and cell apoptosis in high-fat diet plus streptozotocin (STZ)-induced diabetic mice were significantly increased, and these changes were accompanied by a "ghost" peroxisomal phenotype, which was further aggravated in DsbA-L-deficient diabetic mice.

4-Octyl itaconate attenuates LPS-induced acute kidney injury by activating Nrf2 and inhibiting STAT3 signaling.

Background: Septic acute kidney injury (S-AKI) is the leading form of acute kidney failure among hospitalized patients, and the inflammatory response is involved in this process. 4-octyl itaconate (4-OI) is a multi-target itaconate derivative with potent anti-inflammatory action. However, it remains elusive whether and how 4-OI contributes to the regulation of S-AKI.

PACS-2 deficiency in tubular cells aggravates lipid-related kidney injury in diabetic kidney disease.

Background: Lipid accumulation in tubular cells plays a key role in diabetic kidney disease (DKD). Targeting lipid metabolism disorders has clinical value in delaying the progression of DKD, but the precise mechanism by which molecules mediate lipid-related kidney injury remains unclear. Phosphofurin acidic cluster sorting protein 2 (PACS-2) is a multifunctional sorting protein that plays a role in lipid metabolism.

Crescents, an Independent Risk Factor for the Progression of Type 2 Diabetic Kidney Disease.

Context: Crescents have been noticed in pathologic changes in patients with diabetic kidney disease (DKD). However, the clinical significance of crescents is still not well recognized.

Objective: The main objective was to investigate the association between crescents and the prognoses of type 2 DKD (T2DKD) patients, and, secondly, to analyze the relationship between crescents and clinicopathologic features.

PACS-2 Ameliorates Tubular Injury by Facilitating Endoplasmic Reticulum-Mitochondria Contact and Mitophagy in Diabetic Nephropathy.

Mitochondria-associated endoplasmic reticulum membrane (MAM) may have a role in tubular injury in diabetic nephropathy (DN), but the precise mechanism remains unclear. Here, we demonstrate that the expression of phosphofurin acidic cluster sorting protein 2 (PACS-2), a critical regulator of MAM formation, is significantly decreased in renal tubules of patients with DN, and PACS-2 expression is positively correlated with renal function and negatively correlated with degrees of tubulointerstitial lesions. Conditional deletion of Pacs-2 in proximal tubules (PTs) aggravates albuminuria and tubular injury in a streptozotocin-induced mouse model of diabetes.

Norcantharidin inhibits renal interstitial fibrosis by downregulating PP2Ac expression.

Norcantharidin (NCTD) has been proven to be able to attenuate renal interstitial fibrosis, but the exact molecular mechanism is still unknown. This study investigated the relationship between the anti-fibrotic effect of NCTD and its inhibition on PP2Ac expression. Here, PP2Ac was found to be positively correlated with extracellular matrix accumulation in the rat unilateral ureteral obstruction (UUO) model.

[Role of protein phosphatase 2A in renal interstitial fibrosis].

Background: To explore the role of protein phosphatase 2A (PP2A) in renal interstitial fibrosis by using rat model of unilateral ureteral obstructive (UUO) or cell model of human kidney proximal tubular epithelial (HK)-2 cells treated with transforming growth factor-β1 (TGF-β1).


Methods: 1) A total of 15 Sprague-Dawley rats were randomly divided into a sham group, a UUO group and an okadaic acid (OA) treated group (OA group) (n=5 in each group). The OA 
[30 μg/(kg·d)], diluted with 1.

[Role and mechanism of tranilast preventing the progression of tubulointerstilial fibrosis in diabetic kidney diseases].

Objective: To determine the role and mechanism of tranilast preventing the progression of tubulointerstilial fibrosis in diabetic kidney disease (DKD).

Methods: Sprague-Dawley rats were randomly divided into a control group (n=6), DKD model group (n=8), low dose tranilast group [200 mg/(kg.d), n=8], and high dose tranilast group [400 mg/(kg.

Norcantharidin inhibits renal interstitial fibrosis by blocking the tubular epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is thought to contribute to the progression of renal tubulointerstitial fibrosis. Norcantharidin (NCTD) is a promising agent for inhibiting renal interstitial fibrosis. However, the molecular mechanisms of NCTD are unclear.