<p>Calpain-10 drives podocyte apoptosis and renal injury in diabetic nephropathy</p>

Abstract

BackgroundDiabetic nephropathy (DN) is a progressive microvascular complication of diabetes mellitus (DM), driven largely by podocyte apoptosis. The cysteine protease Calpain 10 is known to augment apoptosis and necrosis, and is a potential therapeutic target in DN.MethodsType 2 diabetes was induced in SD rats by high-fat diet (HFD) feeding and streptozotocin (STZ) injections, and simulated in vitro by culturing conditionally immortalized mouse podocytes in hyperlipidemic (PA, 100 μM) conditions. The rate of apoptosis in the renal tissues and cultured podocytes was determined by TUNEL assay. The expression of Calpain 10 and its biological effects were assayed by real-time PCR, Western blotting, immunofluorescence and electron microscopy.ResultsCalpain 10 was up-regulated in the kidneys of DN rats, as well as immortalized mouse podocytes. High levels of Calpain 10 was associated with renal dysfunction and tissue destruction, and podocyte injury and apoptosis. Knockdown of Calpain 10 protected podocytes by decreasing apoptosis rate, and upregulated nephrin.ConclusionCalpain 10 is a pro-apoptotic factor in DN, and can be targeted for treating glomerular diseases.

Trimetazidine Inhibits Renal Tubular Epithelial Cells to Mesenchymal Transition in Diabetic Rats via Upregulation of Sirt1

“…The ultrastructure of the kidney was observed using a transmission electron microscope (TEM; Hitachi, Tokyo, Japan), according to the method described previously (Kalimuthu et al, 2018). Immunohistochemistry and immunofluorescence staining were conducted as described previously (Oshimori and Fuchs, 2012;Wang et al, 2019).…”

Long non‑coding RNA Dlx6os1 serves as a potential treatment target for diabetic nephropathy via regulation of apoptosis and inflammation

“…kidney damage in the early stages by disturbing albumin glomerular excretion as well as renal infiltration (14). Apoptosis-induced dysfunction of podocytes and damage to mesangial cells and renal tubular epithelial cells are indicators of glomerular filtration dysfunction (15)(16)(17)(18). Although the pathology and pathophysiology of DN have been investigated for some time and there has been progress, the complex molecular network is still not fully understood and identification of genes or molecules by conventional tools remains deficient.…”

Exploring the Potential Mechanism of Tang-Shen-Ning Decoction against Diabetic Nephropathy Based on the Combination of Network Pharmacology and Experimental Validation

“…Rats were randomly distributed, after one week of acclimatization, into normal control (NC, n = 6), DN group (DN, n = 6), and TSN group (TSN, n = 6). The DN rat model used in both DN and TSN groups was established as described previously [ 22 ]. Briefly, rats received intraperitoneal injections of streptozotocin (STZ, 55 mg/kg) and a high-fat diet (10% lard, 20% sucrose, 2.5% cholesterol, 0.5% sodium cholate, and 67% basic feed).…”

“…TSN-related DN-DEGs were searched and the dataset Woroniecka Diabetes Glom, which is linked to GSE30528, was selected. [22]. Briefly, rats received intraperitoneal injections of streptozotocin (STZ, 55 mg/kg) and a high-fat diet (10% lard, 20% sucrose, 2.5% cholesterol, 0.5% sodium cholate, and 67% basic feed).…”