Granular vibration pumping system for handling and characterizing particulate materials.

A unique setup for a granular vibration pumping system was developed to ease the installation into a wide variety of granular handling processes and provide flexible options for granular physics research. Although the granular vibration pumping system can notably lift granular materials with an oscillating pipe, the climbing mechanism and related granular physics are yet to be clarified thoroughly. The new setup employs an eccentric cam mechanism as the excitation source, a linear system with dust tolerance, and a recording system, making it simple, compact, and adaptable for extending experiments. The excitation mechanism generated a clear sinusoidal vibration in the pipe, realizing better reproducibility of the climbing motions of glass beads. Moreover, the compact design facilitates the close placement of multiple pipes vibrating individually, which affects the transport performance. In addition, various types of sample cells that store particles and the imaging system allow for the detailed observation of particle motions in the pipes and even the sample cells. This developed system provides easy and accurate tuning of the existing parameters of the granular vibration pumping system, as well as new options for a further understanding of granular physics.

Self-Sufficient Production of Lunar Regolith Gravels on the Moon by Ultrarapid Microwave Sintering.

A sintered lunar regolith is expected to be used to construct buildings, roads, and landing pads for spacecrafts on the Moon. Here, we demonstrate that focused microwave heating is effective for the rapid solidification of the lunar regolith simulant to obtain regolith gravel without any microwave susceptor. The conventional multimode microwave oven cannot heat lunar regolith simulants and requires microwave susceptors such as silicon carbide (SiC) and thermal insulators because of its low dielectric loss. We achieved rapid microwave heating of a lunar regolith simulant without using a susceptor or thermal insulator by forming an intense microwave electric field using a cavity resonator and a semiconductor microwave oscillator. Focused microwaves at 2.45 GHz produced the gravel-shaped and solidified lunar regolith at 300 °C lower temperature than a conventional electrical furnace, where more than 1050 °C temperature was required to sinter the lunar regolith simulant. In addition, we produced larger gravel of the lunar regolith simulant using 915 MHz. The intense electric field generated by the single-mode resonator promoted the solidification of the lunar regolith simulant without any additional substances. This process enables the local production of structured lunar regoliths on the Moon without the transport of any materials from the Earth.

Gross hematuria can be an impact of severe acute respiratory syndrome coronavirus 2 vaccination on immunoglobulin A nephropathy: a case report.

BACKGROUND: Immunoglobulin A nephropathy is typically accelerated by upper respiratory tract infections and can relapse following vaccination. There have been reports of patients who presented with immunoglobulin A nephropathy flares with or without gross hematuria following coronavirus disease 2019 vaccination. However, this relationship remains to be elucidated. CASE PRESENTATION: Herein, we present the case of a patient with newly diagnosed immunoglobulin A nephropathy who presented with gross hematuria following the second dose of coronavirus disease 2019 vaccine. A 21-year-old Japanese woman presented with fever and new-onset gross hematuria 1 day after receiving the second dose of the coronavirus disease 2019 vaccine (Pfizer). She had microhematuria without proteinuria for 2 years at the time of her medical check-up. Gross hematuria resolved 6 days after the second dose of the coronavirus disease 2019 vaccine; however, microhematuria (> 100 per high-power field) and mild proteinuria were observed. She was admitted to our hospital 4 weeks after the second vaccination because of persistent urinary abnormalities. She was well before the vaccination and did not have any pulmonary involvement on chest radiography or any symptoms suggestive of coronavirus disease 2019. Renal biopsy revealed an immunoglobulin A nephropathy. The Oxford MEST-C score was M0E0S0T0C0. Our patient's urinary abnormalities implied exacerbation of immunoglobulin A nephropathy after coronavirus disease 2019 vaccination. CONCLUSIONS: In our case, gross hematuria served as a trigger for immunoglobulin A nephropathy diagnosis, suggesting that nephrologists should pay close attention to gross hematuria and urinalysis after coronavirus disease 2019 vaccination.

In vitro selection of the 3'-untranslated regions of the human liver mRNA that bind to the HCV nonstructural protein 5B.

Hepatitis C virus (HCV) nonstructural protein 5B (NS5B) has RNA-dependent RNA polymerase (RdRp) activity. Because NS5B recognizes various RNA motifs besides the HCV genome, NS5B has the potential of interacting with host RNA molecules. In this study, an RNA pool enriched with the 3'-UTR sequences was generated and mRNA molecules with high affinity binding to NS5B were selected by iterative selection. Among the high binding mRNA 3'-UTR segments, we analyzed the housekeeping ribosomal protein S4, X-linked [RPS4X] mRNA 3'-UTR and the 3'-UTR of galectin-1 (GAL-1) mRNA, which is known to be one of the genes upregulated in HCV-infected liver cells and to have a wide spectrum of biological properties. By means of IP-RT-PCR, it was demonstrated that both of the mRNA molecules bind to NS5B in the cytoplasm. Interestingly, GAL-1 and RPS4X mRNA can serve as templates for NS5B RdRp, suggesting these RNA molecules are regulated in vivo by NS5B.

Comparison of the psychosocial quality of life in hemodialysis patients between the elderly and non-elderly using a visual analogue scale: the importance of appetite and depressive mood.

AIM: The number of hemodialysis (HD) patients is increasing along with their mean age in Japan. The assessment of their psychosocial status and quality of life (QOL) is therefore becoming more and more important along with laboratory data or comorbidities. METHODS: We examined the psychosocial status of 211 HD patients (72 elderly and 139 non-elderly) and compared the difference between elderly and non-elderly patients using a visual analogue scale (VAS). We then examined how QOL affected mortality rate in 3-year prospective follow up. We assessed 10 items of QOL: health condition, appetite, sleep, mood, memory, family relationships, friendship, economical status, life satisfaction in daily life, and happiness with qualified self-evaluating questionnaires along with laboratory data and comorbidities. Furthermore, we investigated the correlation between the scores of mood and geriatric depression scale (GDS)-15. RESULTS: There was no difference in VAS scores between elderly and non-elderly patients. Lower VAS scores for appetite and mood correlated with higher mortality in HD patients, especially in the non-elderly. VAS scores for mood correlated with GDS-15 in HD patients. CONCLUSIONS: More attention should be paid to appetite and the diagnosis and therapy of depressive mood to improve the prognosis of HD patients, especially for the non-elderly.

RNA-dependent RNA polymerase of hepatitis C virus binds to its coding region RNA stem-loop structure, 5BSL3.2, and its negative strand.

The hepatitis C virus NS5B RNA-dependent RNA polymerase (RdRp) is a key enzyme involved in viral replication. Interaction between NS5B RdRp and the viral RNA sequence is likely to be an important step in viral RNA replication. The C-terminal half of the NS5B-coding sequence, which contains the important cis-acting replication element, has been identified as an NS5B-binding sequence. In the present study, we confirm the specific binding of NS5B to one of the RNA stem-loop structures in the region, 5BSL3.2. In addition, we show that NS5B binds to the complementary strand of 5BSL3.2 (5BSL3.2N). The bulge structure of 5BSL3.2N was shown to be indispensable for tight binding to NS5B. In vitro RdRp activity was inhibited by 5BSL3.2N, indicating the importance of the RNA element in the polymerization by RdRp. These results suggest the involvement of the RNA stem-loop structure of the negative strand in the replication process.

Improvement of renal function after opening occluded atherosclerotic renal arteries.

Percutaneous transluminal renal angioplasty (PTRA) with stenting has been effective in the control of hypertension, renal function and pulmonary edema caused by atherosclerotic renal artery stenosis (ARAS). However, concerning the viability of renal function, this procedure has not been fully established, especially in the presence of renal atrophy or severe renal parenchymal disease. We report a dramatically improved case of acute renal failure caused by acute worsening ARAS treated by stenting. A 72-year-old female was admitted for accelerated renal dysfunction (serum ceatinine; 1.2-2.3 mg/dl) and hypertension (190/100 mmHg). At 10 days after admission, the patient's serum ceatinine increased to 6.7 mg/dl, her pulmonary edema was exaggerated and hemodialysis was required. Ultrasonography showed bilateral high-echoic kidneys, but no apparent finding of renal artery stenosis (RAS). At day 15, computed tomographic angiography indicated bilateral ostial RAS. Renal angiography demonstrated total occlusion of the right and severe (90%) disease in the left. ARAS was diagnosed by intravascular ultrasonography. The guidewire was inserted in both renal arteries, PTRA with stenting was performed in the right and a stent was directly implanted in the left. Immediately, each kidney enlarged to almost normal size, leading to satisfactory urination. She was released from hemodialysis the next day since her serum creatinine was normal and the pulmonary edema was improved. Although there is still no reliable prognostic factor including resistive index or kidney size, it is important that PTRA with stenting in ARAS should be considered in a case of accelerated renal dysfunction because of the possible improvement.

In vitro selection of RNA aptamers that bind the RNA-dependent RNA polymerase of hepatitis C virus: a possible role of GC-rich RNA motifs in NS5B binding.

We employed SELEX (systematic evolution of ligands by exponential enrichment) and identified high affinity RNA aptamers to the hepatitis C virus NS5B RNA-dependent RNA polymerase (RdRp). GC-rich stretches were identified in many of the aptamers. Deletion of the 5'-end single-stranded GC-stretch (CGGG) of the highest binding RNA impaired the binding and the inhibitory activity of the RNA to NS5B RdRp. The majority of the mutants with a single base substitution on the CGGG motif exhibited weaker binding to NS5B. Interestingly, the CGGG motif is present on the stem structure of the NS5B coding RNA (5BSL3.2), which is considered to be an important cis-acting replication element. The 5BSL3.2 RNA showed substantial binding to NS5B, while a point mutation on the CGGG motif reduced the binding of RNA to NS5B. These results suggest a GC-stretch to be the RNA element recognized by NS5B.

Acute renal failure after exercise in a Japanese sumo wrestler with renal hypouricemia.

Familial renal hypouricemia is a hereditary disease characterized by extraordinary high renal uric acid clearance and is associated with acute renal failure (ARF). An 18-year-old sumo wrestler developed ARF after anaerobic exercise. Several hours after the exercise, he had a pain in the loins with oliguria, headache, and nausea. On admission, his serum uric acid was decreased despite the elevation of serum creatinine (9.5 mg/dL). The level of creatine kinase was normal and there was no myoglobinuria or urolithiasis. Magnetic resonance imaging showed no significant abnormality. Renal function improved completely within 2 weeks of hydration treatment. After remission, hypouricemia became obvious (1.0 mg/dL) from the initial level of uric acid (6.1 mg/dL) and fractional excretion of uric acid was 49%. Polymerase chain reaction of a urate anion exchanger known to regulate blood urate level (SLC22A12 gene: URAT1) demonstrated that homozygous mutations in exon 4 (W258X). Both parents showed heterozygous mutation of the URAT1 gene, but both siblings showed no mutation. Thus, we describe a Japanese sumo wrestler of familial renal hypouricemia complicated with anaerobic exercise-induced ARF, with definite demonstration of genetic abnormality in the responsible gene, URAT1.

Inhibition of CCR2 ameliorates insulin resistance and hepatic steatosis in db/db mice.

OBJECTIVE: Recently, adipose tissue inflammation induced by macrophage infiltration through MCP-1/C-C chemokine receptor-2 (CCR2) pathway is considered to play a role in the development of visceral obesity and insulin resistance. In the present study, to further examine the role of CCR2 in the development of obesity and type 2 diabetes, we studied the effect of pharmacological inhibition of CCR2 from the early stage of obesity in db/db mice. METHODS AND RESULTS: Db/+m (lean control) and db/db mice were fed with a standard diet with or without 0.005% propagermanium, as a CCR2 inhibitor for 12 weeks from 6 weeks of age. Propagermanium treatment decreased body weight gain, visceral fat accumulation, and the size of adipocytes only in db/db mice. Further, propagermanium suppressed macrophage accumulation and inflammation in adipose tissue. Propagermanium treatment also ameliorated glucose tolerance and insulin sensitivity, and decreased hepatic triglyceride contents in db/db mice. CONCLUSIONS: Propagermanium improved obesity and related metabolic disorders, such as insulin resistance and hepatic steatosis by suppressing inflammation in adipose tissue. Our data indicate that inhibition of CCR2 could improve obesity and type 2 diabetes by interfering adipose tissue inflammation, and that propagermanium may be a beneficial drug for the treatment of the metabolic syndrome.

A model for diabetic nephropathy: advantages of the inducible cAMP early repressor transgenic mouse over the streptozotocin-induced diabetic mouse.

We have previously found progressive diabetic nephropathy in inducible cAMP early repressor (ICER Igamma) transgenic (Tg) mice. The ICER Igamma Tg mouse is an interesting model of sustained hyperglycemia due to its low production of insulin and insulin-producing beta cells. Here in a longitudinal study we further analyzed diabetic nephropathy and structural and functional alterations in other organs, comparing our model with streptozotocin (STZ)-diabetic model mice. The high-dose STZ-diabetic model showed marked variation in blood glucose levels and severe toxicity of STZ in the liver and kidney. The low-dose STZ-diabetic model showed less toxicity, but the survival rate was very low. STZ-diabetic mice had much more variation of glomerular hypertrophy and sclerosis. Furthermore, non-specific toxicity of STZ or insulin injections to maintain optimal blood glucose levels might have another effect upon the diabetic renal changes. In contrast, ICER Igamma Tg mice exhibited a stable and progressive phenotype of diabetic kidney disease solely due to chronic hyperglycemia without other modulating factors. Thus, ICER Igamma Tg mouse has advantages for examining diabetic renal disease, and offers unique and very different perspectives compared to STZ model.

Urinary Smad1 is a novel marker to predict later onset of mesangial matrix expansion in diabetic nephropathy.

OBJECTIVE: We reported that Smad1 is a key transcriptional factor for mesangial matrix expansion in diabetic nephropathy. In this study, we examined whether urinary Smad1 in an early phase of diabetes can predict later development of glomerulosclerosis in diabetic nephropathy and how an angiotensin II type 1 receptor blocker (ARB) can modulate structural changes and urinary markers. RESEARCH DESIGN AND METHODS: Smad1 and albumin in the urine were examined 4 weeks after injection of streptozotocin in 48 rats or 6 weeks of diabetes in db/db mice. Their renal pathology was analyzed after 20 weeks in rats or 12 weeks in mice. Among 48 diabetic rats 7 rats were treated with olmesartan for 20 weeks. RESULTS: Urinary Smad1 of diabetic rats at 4 weeks was nicely correlated with mesangial matrix expansion at 24 weeks (r = 0.70, P < 0.001), while albuminuria showed a weaker association (r = 0.31, P = 0.043). Olmesartan treatment significantly ameliorated glomerulosclerosis and dramatically decreased urinary Smad1 (from 3.9 +/- 2.9 to 0.3 +/- 0.3 ng/mg creatinine, P < 0.05). In db/db mice, urinary Smad1 at 6 weeks was also significantly correlated with mesangial expansion at 18 weeks. In contrast, there was no change in urinary Smad1 in control diabetic rats or mice. CONCLUSIONS: The increase of urinary Smad1 in the early stages of diabetes is correlated with later development of glomerulosclerosis in two rodent models. These data indicate that urinary Smad1 could be a novel predictor for later onset of morphological changes and can be used to monitor the effect of ARBs in diabetic nephropathy.

Inhibition of MCP-1/CCR2 pathway ameliorates the development of diabetic nephropathy.

Monocyte chemoattractant protein (MCP-1) is an important mediator for macrophage recruitment in atherosclerosis and various glomerulonephritis. However, the role of MCP-1 and its receptor CCR2 in the progression of diabetic nephropathy remains unknown. Using a type 1 diabetic nephropathy model that shows noticeable glomerulosclerosis, we examined the role of MCP-1/CCR2 by propagermanium (Pro; CCR2 antagonist) treatment, and confirmed it by transfection of plasmids carrying the 7ND (a mutant of MCP-1) gene. We measured the mesangial matrix expansion, type IV collagen (Col4), transforming growth factor (TGF)-beta1 positive area, and macrophage infiltration in glomeruli after 12 weeks. Mesangial matrix expansion and macrophage infiltration were increased in diabetic mice and inhibited by Pro or 7ND-treatment. Increased glomerular expression of Col4 and TGF-beta1 in diabetic mice was also ameliorated. Thus blocking the MCP-1/CCR2 pathway ameliorated glomerulosclerosis, indicating that the MCP-1/CCR2 pathway plays a crucial role in the progression of diabetic nephropathy.

SRY-related HMG box 9 regulates the expression of Col4a2 through transactivating its enhancer element in mesangial cells.

Accumulation of alpha1(IV) and alpha2(IV) collagen is one of the characteristic pathological changes in glomerulosclerosis. Although the Col4a2 gene is known to have a 0.3-kb critical enhancer element with the GAACAAT motif, which transcription factor binds and transactivates this motif has not been identified. In this study, we found that SRY-related HMG box 9 (SOX9) was bound to the GAACAAT motif in the Col4a2 enhancer in vitro and in vivo in mesangial cells. SOX9 strongly activated this enhancer when cotransfected with Col4a2 enhancer-promoter construct in mesangial cells and Swiss/3T3 cells. Mutation in the GAACAAT motif eliminated the activation by SOX9. Furthermore, transforming growth factor-beta (TGF-beta) treatment induced the expression of SOX9 and Col4a2, and a small interfering RNA against SOX9 reduced Col4a2 expression induced by TGF-beta treatment in mesangial cells. In vivo, we found that the expression of SOX9 was dramatically increased along with the expression of TGF-beta and Col4a2 in mouse nephrotoxic nephritis. These results indicate that SOX9 is essential for Col4a2 expression in mesangial cells and might be involved in the accumulation of alpha2(IV) collagen in experimental nephritis.

Angiotensin II-dependent Src and Smad1 signaling pathway is crucial for the development of diabetic nephropathy.

Angiotensin II (Ang II) is known to play a pivotal role in the development of diabetic nephropathy. However, the precise mechanism of Ang II-mediated effects on diabetic nephropathy is still unknown. We have reported that Smad1 plays a key role in diabetic mesangial matrix expansion and directly regulates the transcription of type IV collagen (Col4) in vitro and in vivo. Here we examined the effect of Ang II on the expression of Smad1 and mesangial matrix expansion in streptozotocin (STZ)-induced diabetic rats in vivo, using Ang II type 1 receptor blocker, olmesartan. We also examined the signaling mechanism by which Ang II induces mesangial matrix expansion in vitro. Treatment of diabetic rats with low-dose olmesartan for 20 weeks reduced albuminuria and hyperfiltration without affecting blood pressure and inhibited mesangial matrix expansive changes and the expression of Col4 and smooth muscle alpha actin compared with those in untreated rats. Immunohistochemical staining and Western blotting showed that the increased expression of Smad1, phospho-Smad1, and phospho-Src was inhibited by olmesartan. Ang II induced Col4 synthesis and increased expression of phospho-Src and phospho-Smad1 in cultured mesangial cells, which was blocked by olmesartan. PP2, a Src tyrosine kinase inhibitor, and overexpression of dominant negative Src also reduced the phosphorylation of Smad1. Moreover, addition of small-interfering RNA against Src significantly reduced the phosphorylation of Smad1 and synthesis of Col4. Taken together, these results indicate that Ang II can regulate the development of mesangial matrix expansion in the early phase of diabetic nephropathy through Src and Smad1.

IgM-immune complex glomerulonephritis associated with sarcoidosis.

We present a case of proliferative glomerulonephritis with peculiar IgM deposition associated with sarcoidosis. A 62-year-old woman, who had been diagnosed with sarcoidosis 3 years previously because of abnormalities on chest X-ray radiophotographs and lymph node pathology, was admitted to our hospital for the evaluation of proteinuria and microscopic hematuria. Laboratory findings showed renal dysfunction (creatinine clearance, 52 ml/min), a moderate range of urinary protein (1.51 g/day), and increased serum lysozymes (20.7 microg/ml; normal range, 3.4-8.6 microg/ml). Serum calcium level was within the normal range. Renal biopsy revealed immune complex glomerulonephritis (IgM deposition type) with a membranoproliferative pattern, without granuloma or calcium deposition. Corticosteroid (initial dose of prednisolone [PSL], 1 mg/kg per day) was administered, but neither renal function nor urinary protein improved. She then became nephrotic and her renal function gradually deteriorated. To our knowledge, among uncommon glomerulonephritides with sarcoidosis, five cases of immune complex glomerulonephritis with IgM deposition have been reported. Immune complex glomerulonephritis with IgM deposition is unusual and could be related to sarcoidosis; it may be a characteristic pathology which could provide a clue to elucidate the pathogenesis of sarcoidosis.

Expression of Smad1 is directly associated with mesangial matrix expansion in rat diabetic nephropathy.

Diabetic nephropathy is the leading cause of end-stage renal disease, and glomerular mesangial matrix expansion is the hallmark in diabetic nephropathy. However, the precise mechanism for the development of mesangial matrix expansion has remained unknown. The key component involved in mesangial matrix expansion is type IV collagen (Col4). Recently, we have reported that Smad1 transcriptionally regulates expression of Col4 under diabetic conditions in vitro. Here we show that this direct regulator of Col4 also plays a crucial role for mesangial matrix expansion in vivo. Streptozotocin-induced diabetic rats are the model of incipient diabetic nephropathy, and showed various levels of mesangial matrix expansion at 24 weeks. The glomerular expression of Smad1 was significantly increased in diabetic rats with more mesangial matrix expansion by Western blot and immunohistochemical analysis. Furthermore, the glomerular expression of Smad1 was closely correlated with the glomerular expression of Col4 and smooth muscle alpha actin (alpha-SMA), while albuminuria or glomerular filtration rate was not correlated with mesangial matrix expansion. We also found that urinary excretion of Smad1 was closely associated with the severity of mesangial matrix expansion. In cultured mesangial cells expression of Smad1 upregulated the transcriptional activity of key molecules in mesangial matrix expansion, such as Col4 and alpha-SMA. These data indicate the critical involvement of Smad1 in mesangial matrix expansion in the early phase of diabetic nephropathy. Our data imply that urinary Smad1 might be a representative diagnostic marker for mesangial matrix expansion in diabetic nephropathy.

Establishment of a diabetic mouse model with progressive diabetic nephropathy.

Although diabetic animal models exist, no single animal model develops renal changes identical to those seen in humans. Here we show that transgenic mice that overexpress inducible cAMP early repressor (ICER Igamma) in pancreatic beta cells are a good model to study the pathogenesis of diabetic nephropathy. Although ICER Igamma transgenic mice exhibit extremely high blood glucose levels throughout their lives, they survive long enough to develop diabetic nephropathy. Using this model we followed the progress of diabetic renal changes compared to those seen in humans. By 8 weeks of age, the glomerular filtration rate (GFR) was already increased, and glomerular hypertrophy was prominent. At 20 weeks, GFR reached its peak, and urine albumin excretion rate was elevated. Finally, at 40 weeks, diffuse glomerular sclerotic lesions were prominently accompanied by increased expression of collagen type IV and laminin and reduced expression of matrix metalloproteinase-2. Nodular lesions were absent, but glomerular basement membrane thickening was prominent. At this point, GFR declined and urinary albumin excretion rate increased, causing a nephrotic state with lower serum albumin and higher serum total cholesterol. Thus, similar to human diabetic nephropathy, ICER Igamma transgenic mice exhibit a stable and progressive phenotype of diabetic kidney disease due solely to chronic hyperglycemia without other modulating factors.

Gas6 induces Akt/mTOR-mediated mesangial hypertrophy in diabetic nephropathy.

BACKGROUND: We have already reported Gas6 is involved in glomerular hypertrophy observed in diabetic nephropathy. However, the molecular mechanisms involved in glomerular hypertrophy are still unknown, especially in vivo. METHODS: In vivo, diabetes was induced in rats and mice by streptozotocin (STZ) and the activation of the Akt/mTOR pathway in glomeruli was examined. In vitro, mesangial hypertrophy was assessed by [(3)H]leucine incorporation and measuring cell areas. RESULTS: Akt, p70 S6 kinase, and 4E-BP-1 were induced and phosphorylated in rat glomerular lysates after 12 weeks of STZ injection when mesangial and glomerular hypertrophy was observed. We then examined the role of Gas6 by treating STZ-rats with warfarin, and found that warfarin treatment inhibited the phosphorylation of these molecules as well as the hypertrophy. We next examined whether high glucose stimulation can induce the expression of Gas6/Axl in mesangial cells. Stimulation of the cells with 25 mmol/L of glucose increased the expression of Gas6/Axl and mesangial cell size compared with that with 5.6 mmol/L of glucose. This hypertrophic effect was abolished in mesangial cells derived from Gas6 knockout mice. We also found that LY294002 and rapamycin blocked Gas6-induced activation of the Akt/mTOR pathway and mesangial hypertrophy. Furthermore, less phosphorylated Akt-positive or 4E-BP-1-positive areas were found in STZ-treated Gas6 knockout mice than in STZ-treated wild-type mice. CONCLUSION: Our study indicates that the Akt/mTOR pathway is a key signaling cascade in Gas6-mediated mesangial and glomerular hypertrophy and revealed a crucial role of Gas6/Axl and the Akt/mTOR pathway in the development of diabetic nephropathy.