Relationship between lysosomal dyshomeostasis and progression of diabetic kidney disease

Abstract

Lysosomes are organelles involved in cell metabolism, waste degradation, and cellular material circulation. They play a key role in the maintenance of cellular physiological homeostasis. Compared with the lysosomal content of other organs, that of the kidney is abundant, and lysosomal abnormalities are associated with the occurrence and development of certain renal diseases. Lysosomal structure and function in intrinsic renal cells are impaired in diabetic kidney disease (DKD). Promoting lysosomal biosynthesis and/or restoring lysosomal function can repair damaged podocytes and proximal tubular epithelial cells, and delay the progression of DKD. Lysosomal homeostasis maintenance may be advantageous in alleviating DKD. Here, we systematically reviewed the latest advances in the relationship between lysosomal dyshomeostasis and progression of DKD based on recent literature to further elucidate the mechanism of renal injury in diabetes mellitus and to highlight the application potential of lysosomal homeostasis maintenance as a new prevention and treatment strategy for DKD. However, research on screening effective interventions for lysosomal dyshomeostasis is still in its infancy, and thus should be the focus of future research studies. The screening out of cell-specific lysosomal function regulation targets according to the different stages of DKD, so as to realize the controllable targeted regulation of cell lysosomal function during DKD, is the key to the successful clinical development of this therapeutic strategy.

Functional characterization of nutraceuticals using spectral clustering: Centrality of caveolae-mediated endocytosis for management of nitric oxide and vitamin D deficiencies and atherosclerosis

“…The combination of these functionalities infers involvement of reciprocal cellular feedback loops that increase NO production and vitamin D3 efficacy, decrease TGF beta signaling and oxidative stress, and activate autophagy. Since down-regulation of TGF beta activity and activation of autophagy is anticipated to intercept/reverse endothelial dysfunction associated diseases including atherosclerosis ( 90 – 93 ), diabetic kidney disease ( 94 – 96 ), and COVID-19 ( 97 – 99 ), supplementation with CM-like functionalities is projected to benefit treatment of these diseases. For validating these effect predictions, clinical trials are warranted.…”

Autophagy and its therapeutic potential in diabetic nephropathy

“…The enhancement of autophagy in proximal tubular epithelial cells (PTECs) in response to multiple stresses such as ischemia and nephrotoxic medications has been reported to protect the kidney ( 71 ). Morphological alterations including hypertrophy, hyperplasia and epithelial-mesenchymal transition (EMT) in RTECs, especially in PTECs, primarily owing to the shortage of autophagy in diabetes, are regarded as an early sign of DN, which can easily cause renal dysfunction and even ESRD if not corrected in time ( 51 , 72 , 73 ).…”

LncRNAs‐circRNAs as Rising Epigenetic Binary Superstars in Regulating Lipid Metabolic Reprogramming of Cancers

“…The PGC1α/CEBPB complex can further promote the expression of CPT1 transcriptionally. [ 142 ] Additionally, lncRNA MACC1‐AS1 has been identified to be elevated in MSC‐cultured gastric cancer cells, which promotes the expression of CPT1 directly through the MACC‐AS1 / miR‐145‐5p/ CPT1 axis possibly. [ 143 ] In a similar way, circ_00 24 107 , also enriched in MSC‐cultured gastric cancer cells, has been identified to mediate lymphatic metastasis of gastric cancer, in which circ_00 24 107 can promote FAO reprogramming by modulating the circ_00 24 107 / miR‑5572 and miR‑6855‑5p/ CPT1A axis.…”

“…This is achieved through the regulation of fatty acid oxidation (FAO) via the miR‐3619‐5p/PGC1α/CEBPB/CPT1 axis. [ 142 ] Moreover, lncRNA MACC1‐AS1 was upregulated in GC cells co‐cultured with MSCs through the TGF‐β/ TGF‐β receptor/SMAD2/3 axis. MACC1‐AS1 then promoted the FAO‐dependent stemness property and chemotherapy resistance of GC.…”