Table 1.
Markers in proximal epithelial tubular cells of S1 and S3 segments and their effects in kidneys
| Renal cell | Marker | Biofunction | Effects in kidneys |
|---|---|---|---|
| PTC S1 segment | Slc5a2 | A major cotransporter for sodium-dependent glucose in kidneys | SGLT2 inhibitors block glucose reabsorption in the proximal tubule and improve systemic glucose homeostasis |
| Slc5a12 | A low-affinity Na( +)-coupled lactate transporter in the initial part of the proximal tubule (S1) | Plasma D-lactic acid levels increased with microalbuminuria and decreased with macroalbuminuria1 | |
| Spp2 | This gene encodes a secreted phosphoprotein that is a member of the cystatin superfamily | SPP2 is associated with kidney development and maturation in mice. In S1P signaling pathway, it has a strong influence on mesangial cell function and DKD progression2 | |
| Slc6a19 | This gene encodes a system B(0) transmembrane protein that actively transports most neutral amino acids (especially methionine) across the apical membrane of epithelial cells | The expression level of this gene is correlated with weight loss, improved glucose tolerance and kidney injury degree in mice3,4 | |
| Gatm | This gene encodes a mitochondrial enzyme that belongs to the amidinotransferase family. This enzyme is involved in creatine biosynthesis, whereby it catalyzes the transfer of a guanido group from L-arginine to glycine, resulting in guanidinoacetic acid, the immediate precursor of creatine | In renal failure, Gatm forms linear aggregation in proximal tubules, impeding mitochondrial division and leading to mitochondrial degeneration, which eventually leads to renal fibrosis and thickening of basement membrane5. Gatm is also associated with serum creatinine content6 | |
| Slc7a7 | The protein encoded by this gene is the light subunit of a cationic amino acid transporter | Slc7a7 is a core gene that controls the renal network, and its methylation level plays a key role in the development of DKD7 | |
| PTC S3 segment | Atp11a | The protein encoded by this gene is an intact membrane ATPase, likely to drive the transport of ions (such as calcium) across the membrane | No related report |
| Ces1f | Ces1f is a member of the carboxylesterase 1 family and is involved in the breakdown of liver cholesterol esters and triglycerides, thereby participating in fat mobilization [8] | No related report | |
| Slc6a18 | Act as specific transporters for neurotransmitters, amino acids, and osmolytes like betaine, taurine, and creatine | No related report | |
| Cyp4a10 | A member of cytochrome P450 | In high glucose environment, Cyp4a will lead to ROS production resulting in apoptosis of podocytes. Inhibition of some cytochrome P450 subtypes can prevent the apoptosis of diabetic podocytes and proteinuria9 | |
| Utp20 | UTP20 is a component of the U3 small nucleolar RNA protein complex and is involved in 18S rRNA processing | No related report | |
| Slc5a8 | This gene functions as a high-affinity sodium-coupled lactate transporter involved in reabsorption of lactate and maintenance of blood lactate level | It could be similar with Slc5a12 |
PTC proximal tubule cell, Slc5a2 solute carrier family 5 member 2 Slc5a12 solute carrier family 5 member 12, Spp2 secreted phosphoprotein 2, Slc6a19 solute carrier family 6 member 19, Gatm glycine amidinotransferase, Slc7a7 solute carrier family 7 member 7, Atp11a ATPase phospholipid transporting 11A, Ces1f: carboxylesterase 1F, Slc6a18 solute carrier family 6 member 18, Cyp4a10 cytochrome P450, family 4, subfamily a, polypeptide 10, Utp20 UTP20 small subunit processome component, Slc5a8 solute carrier family 5 member 8