Epithelium Of Proximal Convoluted Tubules Research Articles

Zuogui-Jiangtang-Yishen decoction prevents diabetic kidney disease: Intervene pyroptosis induced by trimethylamine n-oxide through the mROS-NLRP3 axis

BackgroundNowadays, diabetic kidney disease (DKD) has become one of the most threatening to the end-stage renal diseases, and the early prevention of DKD is inevitable for Diabetes Mellitus (DM) patients. AimsPyroptosis, a programmed cell death that mediates renal inflammation induced early renal injury. The trimethylamine n-oxide (TMAO) was also an independent risk factor for renal injury. Here, the associations between TMAO-induced pyroptosis and pathogenesis of DKD were studied, and the potential mechanism of Zuogui-Jiangtang-Yishen (ZGJTYS) decoction to prevent DKD was further investigated. MethodUsing Goto–Kakizaki (GK) rats to establish the early DKD models. The 16S-ribosomal RNA (16S rRNA) sequencing, fecal fermentation and UPLC-MS targeted metabolism techniques were combined to explore the changes of gut-derived TMAO level under the background of DKD and the effects of ZGJTYS. The proximal convoluted tubule epithelium of human renal cortex (HK-2) cells was adopted to explore the influence of pyroptosis regulated by TMAO. ResultsIt was demonstrated that ZGJTYS could prevent the progression of DKD by regulating glucolipid metabolism disorder, improving renal function and delaying renal pathological changes. In addition, we illustrated that gut-derived TMAO could promote DKD by activating the mROS-NLRP3 axis to induce pyroptosis. Furthermore, besides interfering with the generation of TMAO through gut microbiota, ZGJTYS inhibited TMAO-induced pyroptosis with a high-glucose environment and the underlying mechanism was related to the regulation of mROS-NLRP3 axis. ConclusionOur results suggested that ZGJTYS inhibited the activation of pyroptosis by gut-derived TMAO via the mROS-NLRP3 axis to prevent DKD.

Localization of Canine, Feline, and Mouse Renal Membrane Proteins

Immunohistochemistry allows the localization of proteins to specific regions of the nephron. This article reports the identification and localization of proteins in situ within normal canine, feline, and mouse kidney by immunohistochemistry; maps their distribution; and compares results to previously reported findings in other species. The proteins investigated are aquaporin 1, aquaporin 2, calbindin D-28k, glutathione S-transferase-α, and Tamm-Horsfall protein. Aquaporins are integral membrane proteins involved in water transport across cell membranes. Calbindin D-28k is involved in renal calcium metabolism. Glutathione S-transferase-α is a protein that aids in detoxification and drug metabolism. The role of Tamm-Horsfall protein is not fully understood. Proposed functions include inhibition of calcium crystallization and reduction of bacterial urinary tract infection. The authors' findings in the dog are similar to those in other species: Specifically, the authors localize aquaporin 1 to the proximal convoluted tubule epithelium, vasa recta endothelium, and descending thin limbs; aquaporin 2 to collecting duct epithelium; and calbindin D-28k within distal convoluted tubule epithelium. Glutathione S-transferase-α has variable expression and is found in only the renal transitional epithelium in some individuals, in only the proximal straight tubules in others, or in both locations in others. Tamm-Horsfall protein localizes to thick ascending limb epithelium. These findings are similar in the cat, with the exception that aquaporin 1 is located in glomerular podocytes, in addition to proximal convoluted tubule epithelium, and glutathione S-transferase-α is found solely within the proximal convoluted tubule within all kidney samples examined. The mouse kidney is almost identical to the dog but expresses glutathione S-transferase-α in the glomeruli only.

The effect of shear stress on the basolateral membrane potential of proximal convoluted tubule of the rat kidney

As consequence of glomerular filtration the viscosity of blood flowing through the efferent arteriole increases. Recently, we found that shear stress modulates proximal bicarbonate reabsorption and nitric oxide (NO.) was the chemical mediator of this effect. In the present work, we found that agonists of NO. production affected basolateral membrane potential (V (blm)) of the proximal convoluted tubule (PCT) epithelium. Using paired micropuncture experiments, we perfused peritubular capillaries with solutions with different viscosity while registering the V (blm). Our results showed that a 50% increment in the viscosity, or the addition of bradykinin (10(-5) M) to the peritubular perfusion solution, induced a significant and similar hyperpolarization of the V (blm) at the PCT epithelium of 6 +/- 0.7 mV (p < 0.05). Both hyperpolarizations were reverted by L-NAME (10(-4) M). Addition of 2,2'-(hydroxynitrosohydrazino) bis-ethanamine (NOC-18) 3 x 10(-4) M to the peritubular perfusion solution induced a hyperpolarization of the same magnitude of that high viscosity or bradykinin. These results strongly suggest the involvement of NO. in the effect of high viscosity solutions. This effect seems to be mediated by activation of K+(ATP) channels as glybenclamide (5 x 10(-5) M) added to peritubular solutions induced a larger depolarization of the V (blm) with high viscosity solutions. Acetazolamide (5 x 10(-5) M) added to high viscosity solutions induced a larger hyperpolarization (8 +/- 1 mV; p < 0.05), suggesting that depolarizing current due to HCO(-)3 exit across the basolateral membrane damps the hyperpolarizing effect of high viscosity. Considering that Na(+) and consequently water reabsorption is highly dependent on electrical gradient, the present data suggest that the endothelium of kidney vascular bed interacts in paracrine fashion with the epithelia, affecting V (blm) and thus modulating PCT reabsorption.

Morphological changes in lungs, placenta, liver and kidneys of pregnant rats exposed to cigarette smoke.

Histopathological examination of changes in foetal and newborn rats, and histopathological and morphometric assessments of changes in lungs, placenta, liver and kidneys of adult rats exposed to cigarette smoke were performed. Non-pregnant and pregnant Wistar female rats were exposed to cigarette smoke at a carbon monoxide concentration of 1500 mg/m(3) for 6 h per day, 5 days per week, for 3 weeks. Levels of urine nicotine and cotinine were used as measures of exposure. Paraffin-embedded, haematoxylin and eosin (HE)-stained sections were used for examination. Morphometry of studied organs was performed using a computer image analyser. Applied smoke dose and exposure time produced dramatic histopathological changes in lungs of exposed rats (emphysema, emphysematous, inflammatory, metaplastic changes) and reduction in height of respiratory-bronchiole epithelium, and considerably less-marked morphological changes in hepatic (number of apoptotic hepatocytes) and renal (height of proximal convoluted tubule epithelium) cells as well as in the placenta (for example, size of giant cells in labyrinth, height of epithelium covering yolk sac ). Exposure to cigarette smoke did not result in histopathological changes in lungs and liver of surviving foetuses. The duration of pregnancy was not changed but a tendency for a decrease in the mothers' fertility indices as well as some changes in foetal and newborn parameters was observed. Taking into account the morphological changes observed in adult rat tissues and placentae which can result in definite hormonal and trophic effects on the foetus, the possibility of early or late physiological effects in progeny under the influence of cigarette smoke must be taken into consideration.

Ia antigens in rat kidney, with special reference to their expression in tubular epithelium.

The distribution of Ia antigens in rat kidneys has been investigated by an immunoperoxidase technique, using monoclonal antibodies directed at framework determinants on molecules equivalent to gene products of the I-A and I-E/C regions of the mouse major histocompatibility complex (MHC). Antigens mapping to both loci were detected in proximal convoluted tubule epithelium and on scattered dendritic cells in the interstitial connective tissues, glomeruli, and mucosa of the renal pelvis. All other structures were negative. Genetic studies indicate that the levels of expression of Ia molecules from both genetic loci are controlled by non-MHC genes in epithelium, but not on lymphocytes. The subcellular distribution of Ia molecules has been investigated in tubular epithelium and is discussed in relation to their possible functions in epithelia.

Kidney Alkaline Phosphatase of Rats Following Alloxan Induced Diabetes and Acute Hypo- and Hyperglycemia

Summary1. The alkaline phosphatase activity of the rat kidney, which reflects principally the enzyme content of the proximal convoluted tubules, could not be changed from the normal by varying the amount of glucose for reabsorption over periods of 6 to 12 hours.2. The kidneys of rats suffering from chronic alloxan diabetes as a rule contained less than normal amounts of alkaline phosphatase. The lowest values were obtained when first examined one week after the dose of alloxan, but recovery of a normal content was not complete when the last examination was performed after 42 days. The proximal convoluted tubule epithelium that had regenerated after the alloxan injury was thus observed to be slow in acquiring its normal enzyme content.

THE FUNCTIONAL AND PATHOLOGICAL RESPONSE OF THE KIDNEY IN DOGS SUBJECTED TO A SECOND SUBCUTANEOUS INJECTION OF URANIUM NITRATE

The present study permits the following conclusions. 1. Uranium nitrate in the dog has a high degree of selective affinity as a nephrotoxic for the epithelium of the proximal convoluted tubules. The glomeruli participate in the injury and develop obliterative connective tissue changes as evidence of a preexisting acute injury followed by repair. 2. The repair to the degenerated tubular epithelium is accomplished by two processes. First, by a regeneration of convoluted tubule cells from such cells not too severely injured in this location. This type of regenerated epithelium has no resistance to uranium. Second, the regeneration may occur as an ingrowth of cells or as syncytial buds from cells in the terminal portion of the proximal convoluted tubule or from the upper end of the descending limb of Henle's loop. This type of regenerated epithelium which is entirely different cytologically from normal convoluted tubule epithelium is resistant to a second injury from uranium even when the amount of this nephrotoxic agent has been increased to double the amount of the initial injection. 3. The kidney does not develop a local tissue immunity or resistance to uranium in the sense that cells of the same type once injured by it acquire as a result of the injury a resistance. The resistance and apparent but not real immunity is due to another type of cell with resistance having been substituted for a cell with but little resistance. This fact may be looked upon as constituting part of a defense mechanism in the kidney and may in part explain the long duration of certain types of chronic nephritic processes. 4. The functional studies which have been made during the initial injury from uranium to the tubules and during the secondary injury in animals which have either shown a resistance or a lack of resistance, emphasize the importance of the tubular epithelium as a part of a secretory mechanism in urine formation. During periods when the proximal convoluted tubule epithelium is in a state of acute degeneration there is a disturbance in the acid-base equilibrium of the blood, a reduction in the elimination of phenolsulphonephthalein and a retention of urea nitrogen, non-protein nitrogen and creatinine. When this epithelium is regenerated by the formation of a tubular epithelium normal in character for this location of the tubule, regardless of structural changes in the glomeruli, the above evidence of renal dysfunction returns to the normal. If at such a period this type of regenerated epithelium be injured by a secondary injection of uranium a state of acute renal dysfunction is induced in an intensified form. In those animals in which the repair to the tubules was accomplished by the formation of an atypical type of epithelium in the convoluted tubules as well as by the formation of cells normal in histological appearance for this part of the tubule there was an improvement in the degree of depletion of the reserve alkali of the blood, in the elimination of phenolsulphonephthalein and in the retention of urea nitrogen, non-protein nitrogen and creatinine. Certain of these values did not reach the normal. In such a state of renal repair when a second injection of uranium was given the kidney was found to have developed a marked resistance to it. There was but slight evidence of a depression in renal function. Associated with this acquired functional resistance there was no evidence of injury to the atypical, flattened regenerated epithelium of the proximal convoluted tubules.