Study of different expression profiles of "transient receptor potential ion channel (TRPC) gene family" in patients undergoing renal biopsies with clinically suspected glomerulonephritis

Glomerular kidney diseases continue to affect a large number of people around the world and are involved in etiologies leading to recent kidney disease. The earliest sign of these diseases is the loss of protein in urine. Podocytes, a component of the glomerular filtration barrier, play an important role in studies on proteinuria mechanisms. Podosit, and congenital nephrotic syndrome (proteins Nesrin slit from diagram, Podolski, CD-2 associated protein, the result of mutations in trpc6), minimal lesion disease (MLH), focal segmental glomerulosclerosis (FSGS), Membranous Glomerulonephritis (MGN), lupus nephritis, and experimental glomerular diseases such as diabetes and has suffered damage in many human. Depending on the severity and duration of the damage, podocytes can respond differently. Autophagy and hypertrophy (stage I) seen in early stage podocytes are adaptive and protective. However, as the severity and length of the damage increases in later stages (stages II and III) maladaptive process is entered and clinically proteinuria is observed and pathologically the event progresses from epithelial to mesenchymal cells after the transition to apoptitosis and ultimately glomerulosclerosis. TRPC channels are non-selective Ca + 2 permeable cation channels and are widely expressed in the tissues of vertebrates. They become active in response to signal transduction pathways associated with phospholipase C alert. The transient receptor potential ion channel C6 (TRPC6) is expressed in podocytes and is a component of the slit diaphragm. Trpc6 is associated with slit diaphragm proteins in podocytes (such as nephrin, podosin, α-actinin-4) and mechanosensitive Ca+2-activated K+ channels. In genetic and acquired diseases, TRPC6 overactivation causes podocyte damage by pathological CA + 2 entry. Dual is effective. Its acute activation protects podocytes from complement-mediated damage, while its chronic activation leads to Focal segmental sclerosis. Trpc6 has been observed to activate calcineurin in cultured podocytes. Calcineurin activation leads to proteinuria by dephosphorylation in podocytes and proteolysis of the actin-associated protein synaptopodine. TRPC1, TRPC2, TRPC4, and TRPC5 interact with a protein called stromal-interacting molecule 1 (STIM 1), which is susceptible to intracellular calcium storage content. As a result of binding with this protein, TRPC channels bind to calcium-releasing shingles in endosomes. STIM1 does not bind to TRPC3 or Trpc6, but they indirectly change the gate behavior of TRPC channels in different cell types. It is not known whether STIM1 exprese in podocytes. Apart from the fact that the trpc6 gene mutation is the cause of hereditary focal segmental sclerosis (FSGS), pathophysiologically increased trpc6 expression levels have also increased in acquired glomerular diseases. In our study, the genetic origin of the mRNA expression of TRPC6 non-minimal lesion disease (MLH) and Membranous Glomerulonephritis (MGN) in renal biopsy samples of patients in the control group patient samples (tumor, healthy part of the kidney nefrektomil of patients) compared with has increased significantly. Based on this, it is said that Trpc6 plays an important role in non-genetic glomerular diseases and that the blockages that can be made for Trpc6 can be an effective treatment method. The aim of the study was to contribute to the diagnosis and prognosis of patients with clinically considered glomerulonephritis by examining different expression profiles of TRPC family members in renal biopsy specimens. Material Method: This study was conducted with 108 patients admitted to Ege University Faculty of Medicine Nephrology Clinic who underwent a kidney biopsy with a preliminary diagnosis of glomerulonephritis and 37 patients who underwent a nephrectomy in urology clinic with a diagnosis of primary kidney tumor as a control case. PKD2, TRPC1, TRPC6, STIM-1 and Orai-1 mRNA levels were studied in the biopsy samples. Results: When we compared the patient and the control group, the gender distribution of both groups was similar. The frequency of diabetes and hypertension was similar. When we compared the TRPC expression profiles of the patient and the control group, the TRPC expression levels of the renal biopsy group were statistically significantly higher than those of the control group. When we performed subgroup analysis, the TRPC1, TRPC6 and STIM1 levels of the diabetic group were statistically significantly higher compared to the non-diabetic group of patients with and without diabetes. There was a positive correlation between TRPC1, TRPC6 and STIM1 and the presence of diabetes in the correlation analysis of the patient group. There was a positive correlation between arteriolar hyalinosis and NPHS2 and ORAI in the biopsy. Interestingly, there was a negative correlation between TRPC6, NPHS2 and PKD2 and IG M positivity.There was a negative correlation with TRPC6 and STIM1 levels with positive C4D staining of glomeruli in renal biopsy. Positive correlation was found between ORAI and glomerular sclerosis rate. As a result, we found that TRPC gene expression profiles in proteinuric kidney patients were statistically significantly increased compared to healthy kidney tissue, which supported the relationship between increased TRPC6 expression and proteinuria in the literature. We did not find a positive relationship between proteinuria severity and TRPC expression profiles. Again, when we looked at our results, similar to the literature, we found that TRPC6 and STIM1 expression profiles were increased in diabetic patients, which supports the knowledge that intracellular calcium pathways were activated in podocyte damage.