Increased Epidermal Growth Factor Expression Research Articles

Genetic polymorphism of epidermal growth factor gene as a predictor of hepatocellular carcinoma in hepatitis C cirrhotic patients

ObjectivesTo investigate the correlation between the epidermal growth factor (EGF) polymorphism and the risk of hepatocellular carcinoma (HCC) in hepatitis C viral (HCV)-related cirrhotic patients as well as its relation to EGF protein expression in HCC tissue.BackgroundIn Egypt, the incidence of HCC is ∼4.7% in chronic liver disease patients because of HCV infection. EGF plays an important role in hepatocyte regeneration and also plays a role in malignant transformation. A functional polymorphism in EGF was identified recently as the G/G genotype was associated with a higher risk of HCC and increased EGF expression in serum and liver tissue from HCC patients.Patients and methodsThis case–control study was carried out on 100 patients in the HCC clinic of the National Liver Institute, Menoufia University. Routine investigations and EGF genotyping were performed in 50 HCC patients (group I) subdivided into 25 patients with resectable HCC (subgroup IA) and 25 patients with advanced unrespectable HCC (subgroup IB). Twenty-five cirrhotic HCV patients did not have HCC (group II). There were a total of 25 healthy individuals (group III). Immunohistochemical detection of EGF was performed in HCC tissue biopsy from patients who underwent surgical resection.ResultsThe GG genotype was associated with a significantly increased risk of HCC compared with the AG and AA genotypes (P = 0.031) in the cirrhotic group. The G allele led to a highly significant risk of HCC compared with allele A in recessive model GG versus AG + AA (P = 0.036) rather than in the dominant model GG + AG versus AA (P = 0.66). EGF expression in tumor tissue was statistically different only between GG and AG genotypes in the resectable HCC group (group IA) (P = 0.032).ConclusionThe EGF gene polymorphism (GG genotype) led to a significant risk of HCC development in cirrhotic patients more than the AG and AA genotypes.

Genetic Polymorphism of Epidermal Growth Factor Gene as a Predictor of Hepatocellular Carcinoma in Hepatitis C Cirrhotic Patients.

Background:In Egypt, the incidence of hepatocellular carcinoma (HCC) is approximately 4.7% of chronic liver disease patients due to (HCV) infection. Epidermal growth factor (EGF) plays an important role in hepatocyte regeneration. A functional polymorphism in EGF 61A>G was identified; itwas associated with higher risk of HCC. Objectives:to investigate the correlation between the epidermal growth factor (EGF) polymorphism and the risk of hepatocellular carcinoma (HCC) in hepatitis C viral (HCV) cirrhotic patients as well as its relation to EGF protein expression in HCC tissue. Patients and methods:this casecontrol study was conducted on 75 HCV cirrhotic patients including 50 HCC patients (25 withresectable HCC and 25 with advanced unresectable HCC) and 25 healthy persons were included. EGF genotype was detected by restriction fragment length polymorphism. EGF expression in HCC tissue biopsiesfrom patientswhounderwent surgical resection was done by immunohistochemical examination. Results:The GG genotype was associated with significant increased risk of HCC compared to AA genotypes (P=0.031) in cirrhotic group. The G allele had a highly significant risk of HCC compared to allele Ain recessive model GG vs. AG+AA (P=0.036) rather than in the dominant model GG +AG vs. AA (P=0.66). There was significant increased expression of EGF in tumour tissues in patients with GG genotype compared to AG genotype and AA genotype p= 0.019. Conclusion: EGF gene polymorphism (GG genotype) had a significant risk of HCC development in cirrhotic patients. This is confirmed by increased EGF expression in liver tumor tissue from HCC patients.

The Effect of Human Bone Marrow Mesenchymal Stem Cells on Epidermal Growth Factor and Epidermal Growth Factor Receptor Expression in Re-epithelialization Process in the Healing of Burns on Experimental Rats

BACKGROUND: Research on human bone marrow mesenchymal stem cells (hBM-MSCs) for burns healing has been known to increase the percentage of integrin expression of α2β1, type I collagen, transforming growth factor-β, and matrix metalloproteinases-9, but research on giving hBM-MSCs to growth factor expression in the process of re-epithelialization of burn healing has not been done.
 AIM: This study aims to the effect of hBM-MSCs given on the expression of epidermal growth factor (EGF) and EGF receptor (EGFR) in the process re-epithelialization in the healing of burn experimental rat.
 MATERIALS AND METHODS: This research is experimental with the post-test only control design, using 30 Wistar rats. Rats were divided into two groups, namely, control (phosphate-buffered saline), and the treatment was given hBM-MSCs, and stem cells were given subcutaneous doses of 2 × 106 cells/ml. Before being treated rats were anesthetized using xylazine and ketamine then the rats were burned in the dorsal (spine) with full-thickness. On the 3, 7, and 14 days, skin tissue was taken to see the expression of EGF and EGFR by immunohistochemical methods. This study was approved by the Ethics Commission of the Faculty of Medicine, Andalas University, Padang. The results of the study were analyzed by the t-test.
 RESULTS: Immunohistochemical examination of EGF and EGFR expressions after hBM-MSCs administration has significantly increased epithelialization compared with controls. Increased EGF expression was found on days 3 and 7 with moderate positive internal revenue service (IRS) assessment and on day 14 strong positive EGF expression, as well as EGFR expression on days 3 and 7 with moderate positive IRS assessment and on day 14 robust positive EGFR expression.
 CONCLUSION: This study concluded that giving of hBM-MSCs can increase the expression of EGF and EGFR which enhances the process of re-epithelialization thereby accelerating the healing of burns of experimental rats.

Resveratrol modulates intestinal morphology and HSP70/90, NF-κB and EGF expression in the jejunal mucosa of black-boned chickens on exposure to circular heat stress.

The aim of this study was to investigate whether supplementation with resveratrol could alleviate intestinal injuries and to explore how resveratrol regulates heat shock protein (HSP)70, HSP90, nuclear factor kappa B (NF-κB) and epidermal growth factor (EGF) expression in the jejunal mucosa of black-boned chickens under circular heat stress. A total of 300 black-boned chicks of 42-d-old were randomly assigned to five treatment groups. The positive control chickens were kept in a normal-temperature (NT, 24 ± 2 °C) chamber and fed with a basal diet. The other four groups were kept in a circular high-temperature (HT, 37 ± 2 °C) chamber for 8 h and fed a basal diet supplemented with 0, 200, 400, or 600 mg per kg of resveratrol for 15 days. The results showed that the heat-stress responses damaged the villus structures of the jejunum and ileum, resulting in shortened intestinal villi, deepened crypts, and a reduced villus height to crypt depth (V/C) ratio and decreased the numbers of goblet cells and lymphocytes. Heat stress also caused increased mRNA and protein expression of HSP70, HSP90 and NF-κB, and reduced EGF in the jejunal mucosa. Dietary supplementation with 400 mg per kg of resveratrol improved the villus morphology, increased the numbers of goblet cells and lymphocytes, attenuated the mRNA overexpression of HSP70, HSP90 and NF-κB on the 6th, 10th and 15th day of heat stress (P < 0.05), and activated the expression of EGF (P < 0.05) in the jejunal mucosa. Resveratrol reduced protein expression of HSP70, HSP90 and NF-κB in the jejunal villi after 15 days of heat stress, and increased EGF expression from the lamina propria toward the epithelial cells of the villi. These results suggest that dietary resveratrol offers a potential nutritional strategy to improve the intestinal morphology and alleviate jejunum mucosa injuries by modulating the mRNA and protein expression of HSPs, and the epithelial growth factor and transcription factor in black-boned chickens subjected to circular heat stress.

Abstract 3592: Macrophages confer resistance to cisplatin in MTLn3 and MDA-MB 231 breast cancer cells

Abstract Drug resistance presents a clinical challenge to the treatment of breast cancer. Stromal cells such as macrophages may play a role in drug resistance. The purpose of this study is to examine the interaction between breast cancer cells and macrophages and its effects on drug therapy resistance. The five-year survival for localized hormone sensitive disease is 98% and as low as 15% for triple negative (ER/PR/Her2) and metastatic disease. Most targeted anticancer therapies, as well as cytotoxic therapies, are burdened by the development of cancer cell resistance. It is hypothesized that the tumor microenvironment may confer innate resistance to drug therapy. It is well established that chemotactic factors found in the tumor microenvironment can promote motility and invasion. We hypothesize that tumor associated macrophages can confer drug resistance to breast cancer cells via overexpression of epidermal growth factor (EGF). EGF is overexpressed in many tumor types and is clinically correlated with a poor overall prognosis. Previous studies have shown that EGF is produced by non-tumor cells in the microenvironment; in particular tumor-associated macrophages (TAM) and endothelial cells. We have previously shown that macrophages and tumor cells, via a paracrine loop, are necessary and sufficient for comigration and invasion. Breast cancer cells produce colony stimulating factor 1 (CSF-1) which positively feeds back to increase macrophage expression of EGF. Increased EGF expression in turn leads to tumor growth and invasion. We selected two triple negative breast cancer cell lines, MDA-MB 231 (human mammary adenocarcinoma) and MTLn3 (rat mammary adenocarcinoma) that were transfected to express GFP. Co-culture cell survival assays were performed with macrophages, fibroblasts, and endothelial cells. All tissue culture was completed in DMEM (HyClone) plus 10% FBS. Cells were grown for 24 hours in co-culture, treated with chemotherapy (doxorubicin or cisplatin at a range of concentrations) for 24 hours, and then analyzed at 72 hours using the DXP-10 Calibur analyzer. Prior to analysis, cells were again replated to measure “replating efficiency” i.e. chemoresistant cell survival. We found that coculture with macrophages increased tumor cell survival upon exposure to cisplatin. We conclude that macrophages are an important component of the tumor microenvironment that may play a role in chemotherapy resistance. Citation Format: Joshua K. Sabari, Ramon Cabrera, Jeffrey Segall. Macrophages confer resistance to cisplatin in MTLn3 and MDA-MB 231 breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3592. doi:10.1158/1538-7445.AM2014-3592

Functional and Histologic Changes in the Lacrimal Gland After Botulinum Toxin Injection

The purpose of this study was to evaluate changes in tear volume, epidermal growth factor (EGF), and histology of the rabbit lacrimal gland after intraglandular application of botulinum toxin. Ten New Zealand rabbits were separated into 3 groups. Eight rabbits received botulinum toxin injection (2.5 U per 0.1 mL) into the right lacrimal gland and saline injection (0.1 mL) into the left lacrimal gland as a sham control. Two rabbits were untreated to serve as normal controls. Tear volume was measured using cotton thread every 2 weeks, and 4 rabbits were killed after 2 and 4 weeks. The lacrimal glands were surgically excised and sectioned or lysed for gene expression analysis. Epidermal growth factor expression and concentration were evaluated by real-time polymerase chain reaction and enzyme-linked immunosorbent assay; morphometric and histologic analyses were performed. The rabbits that were killed 2 weeks after the injection showed decreased tear volume and increased EGF expression and concentration, but differences were not statistically significant. The rabbits that were killed 4 weeks after the injection exhibited similar results. When all 8 rabbits were considered, we detected a significant decrease in tear volume and increased EGF expression and concentration (P = 0.012, P = 0.011, and P = 0.012, respectively). The EGF level was not significantly correlated with the tear volume. There were no prominent histologic changes between the glands, and the lumen versus fibrosis ratio in the interlobular ducts showed no statistically significant difference. The use of botulinum toxin in patients with epiphora is effective, safe, and repeatable because it reduces tear volume and increases the EGF level to prevent corneal damage while causing no histologic changes.

EGF mediates aldosterone‐induced regulatory effects of myofibroblasts on the junctional permeability of cultured colonic epithelial cells

Aldosterone (ALDO) regulates the growth of pericryptal myofibroblasts and the permeability of the colonic epithelium in vivo. We have examined whether these effects of ALDO can be reproduced in vitro, using the myofibroblast CCD-18Co cell line to study proliferation and the colonic epithelial cell line T84 to study the expression of tight junction proteins. The possible role of the epidermal growth factor (EGF) as mediator of myofibroblasts effects on the expression of junctional proteins was also studied. Cell proliferation was quantified from bromodeoxyuridine incorporation, the expression of tight-junction proteins β-catenin and claudin IV by Western blot and EGF expression by RT-PCR. ALDO stimulated CCD-18Co proliferation by 70% (P<0.05) and increased EGF expression (P<0.05), and both effects were prevented by Spironolactone. ALDO had no direct effects on the expression of junctional proteins by the T84 cells; however, both β-catenin and claudin IV were increased when the T84 cells were incubated with medium from myofibroblasts stimulated by ALDO (conditionated medium, CM). The CM increased 40% (P<0.05) T84 proliferation and about 30% (P<0.05) the expression of β-catenin and claudin IV and these effects were prevented by anti-EGF antibodies. These results indicate that EGF is a candidate to mediate the ALDO effects on crypt epithelial permeability. Supported by BFU2006-08410, MEC, Spain.

The effect of epidermal growth factor in the injured brain after trauma in rats.

Epidermal growth factor (EGF) is a known mitogen for neural stem and progenitor cells (NS/NPCs) in the central nervous system (CNS). In vitro, EGF maintains NS/NPCs in the proliferative state, whereas in the normal rodent brain it promotes their proliferation and migration in the subventricular zone (SVZ). Additionally, EGF administration can augment neuronal replacement in the ischemic-injured adult striatum. Recently we found that the SVZ and the hippocampus display an injury-induced proliferative response following traumatic brain injury (TBI) that is linked to increased EGF expression. As adult neurogenesis is associated with cognitive function, we hypothesized that post-TBI administration of EGF could affect neurogenesis and cognitive recovery. Adult rats were intraventricularly infused with EGF or vehicle for 7 days following TBI. 5-Bromo-2-deoxyuridine (BrdU) was administered to label proliferating cells and the animals were sacrificed at 1 or 4 weeks post-injury. Using immunohistochemistry and stereology, we found that at 1 week post-injury, compared to vehicle-infused animals EGF-infused animals had significantly more BrdU-positive cells in the SVZ and hippocampus concomitant with enhanced EGF receptor expression. At 4 weeks post-injury, the number of BrdU-positive cells in the hippocampus was similar in both groups, suggesting that EGF does not support long-term survival of newly generated cells. Furthermore, we found that the EGF-induced proliferative population differentiated preferentially toward astroglial phenotype. Nevertheless, animals treated with EGF showed significant improvement in cognitive function, which was accompanied by reduced hippocampal neuronal cell loss. Collectively, the data from this study demonstrate that EGF exerts a neuroprotective rather than neurogenic effect in protecting the brain from injury.

Influences of bFGF and EGF on the proliferation and differentiation of endogenous neural stem cells after cerebral infarction in human

To investigate the relationship of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) and proliferation of endogenous neural stem cells (NSCs) after human cerebral infarction. Paraffin-embedded brain tissues of 22 human fatal cases of CI from the brain tissues around subventricular zone and subgranular layer zone were stained with HE and immunohistochemistry stain. The endogenous neural stem cells were marked by nestin. The expression changes of EGF, bFGF and nestin in the perihematomal tissues were analysed with the SPSS 13.0 system. (1) Compared with the controls, the number of nestin-positive cells increased at 24 - 72 h (14 +/- 6)/HP in the ipsilateral SVZ and began to rise at 4.5 - 10 h (11 +/- 5)/HP in the ipsilateral SGZ, reached maximum at 120 - 144 h ((38 +/- 7)/HP in the SVZ, (54 +/- 17)/HP in the SGZ, and decreased markedly at 216 - 336 h, but it was still elevated compared with the controls (P < 0.05). (2) The number of bFGF-positive cells increased at 4.5 - 10 h (8.1 +/- 2.9)/HP in the SVZ, (19.0 +/- 8.2)/HP in the SGZ, reached maximum at 24 - 70 h (15.6 +/- 3.5)/HP in the SVZ, (32.0 +/- 5.7)/HP in the SGZ and decreased at 72 - 96 h, but it was still elevated compared with the controls (P < 0.05). (3) The number of EGF-positive cells increased at 4.5 - 10 h (4.3 +/- 1.6)/HP in the SVZ, (7.0 +/- 3.7)/HP in the SGZ, reached maximum at 120 - 144 h (27.0 +/- 1.4)/HP in the SVZ, (51.5 +/- 4.9)/HP in the SGZ and decreased at 216 - 336 h, but it was still elevated compared with the controls (P < 0.05). Perhaps the increased expression of EGF and bFGF after CI was a reaction of endogenous reparation and it correlated with the proliferation and endogenous of neural stem cells in human.

Cloning of Novel Epidermal Growth Factor (EGF) Plasmid for Gene Therapy on Diabetic Foot Ulcer

Background: Epidermal Growth Factor (EGF) is one of the important growth factors involved in the epithelialization during cutaneous wound healing. Peptide EGF has been used for the treatment of diabetic foot ulcer. But the inferiority of cost-effectiveness and the inconvenience of daily application might have restricted its wide clinical usage. EGF gene therapy could dram atically improve the efficacy and inconvenience through long-term expression and bypassing the EGF degradation by hostile non-specific proteinases expressed in the wound bed. Methods: EGF DNAs were amplified via PCR. For the more effective secretion from the transfected cell, we inserted furin cleavage site into EGF plasmids. The efficacy of novel plasmid pβ -EGF was verified by transfection into the various animal cell lines, and the biologic potency of expressed EGF was confirmed via phosphorylation of PI3K and GSK3β by Western blotting. Results: We tested various kinds of human EGFs. One of the human EGF isoforms, EGF 828 including a membrane-anchoring domain was su ccessfully released as the matu re EGF protein in the cell culture media. Also EGF plasmid including furin cleavage site showed more than 2-fold increased EGF expression compared with the sequence without furin cleavage site. Conclusion: In conclusion, these findings suggest that mature EGF could be released easily out of cells by modifying EGF DNA sequence. Our novel EGF plasmid DNA could markedly increase the efficiency of non-viral gene therapy for diabetic foot ulcer. (KOREAN DIABETES J 32:131~140, 2008)

Possible mechanisms explaining the tendency towards interstitial fibrosis in aristolochic acid-induced acute tubular necrosis

We explored possible mechanisms responsible for the inability of plerosis and the tendency towards fibrosis in aristolochic acid-induced acute tubular necrosis (AA-ATN). Renal biopsy tissues from eight AA-ATN cases were examined. Tubulointerstitial injury was semiquantitatively assessed. Immunohistochemical steptavidin-peroxide (SP) methods were used to determine the expressions of proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF), alpha-smooth muscle actin (alpha-SMA), transforming growth factor-beta(1) (TGF-beta(1)), connecting tissue growth factor (CTGF), fibronectin (FN), collagen III (Col-III), collagen IV (Col-IV), factor VIII-related antigen (VIII-Ag) and vascular endothelial growth factor (VEGF). Ultramicrostructure of endothelial cells and basement membrane of peritubular capillaries (PTC) and glomerular capillaries was detected by electron microscopy. These data were compared with that of 9 cases of antibiotic-induced ATN (a-ATN) and 10 cases of minor mesangioproliferative non-IgA glomerulonephritis, which served as a control group. In AA-ATN, almost no renal tubular epithelial cells (RTEC) were PCNA-positive (0.01 +/- 0.02%), and EGF expression was considerably decreased (9.55 +/- 7.22%). This was in contrast with the highly active tubular proliferation (PCNA-positive RTEC 47.25 +/- 19.33%, P < 0.05) and increased EGF expression in a-ATN (64.38 +/- 19.22%, P < 0.05). The expression of alpha-SMA in the tubulointerstitium, the number of interstitial TGF-beta(1)-positive cells and the CTGF-positive interstitial area were all increased in both a-ATN and AA-ATN, with no obvious differences between the two groups. With respect to extracellular matrix (ECM) deposition, FN, Col-III and Col-IV were detected only in the interstitium of AA-ATN. PTC lumina were decreased in size and misshapen in the AA-ATN group. Also in AA-ATN, the luminal wall was partially disrupted, endothelial cells were swollen and vacuoles and granules were found in the cell plasma. Parts of the endothelial cells were detached from the tubular basement membrane. The strong ability for RTEC repair after acute injury was severely diminished in AA-ATN, and this effect may be partly due to reduced EGF expression. Anti-fibrosis mechanisms may also be impaired in AA-ATN, since both a-ATN and AA-ATN had increased expression of TGF-beta(1) and CTGF, whereas only the latter group showed ECM deposition. Injury and loss of PTC occurred in AA-ATN, and this may contribute to tubulointerstitial damage, the inability of plerosis and the tendency towards fibrosis in this disease.

EGF gene polymorphism and the risk of incident primary melanoma.

Overexpression of the epidermal growth factor (EGF) pathway has been implicated in melanoma pathogenesis, and a recent case-control study identified a single nucleotide polymorphism (G to A) in the EGF gene where the G allele was associated with increased EGF expression and an increased risk of melanoma. To further evaluate this association, we conducted a case-control analysis from the Genes, Environment, and Melanoma study at the University of Michigan site using two different study designs. Incident cases of histopathologically confirmed first primary melanoma that were diagnosed between January 1, 2000 and December 31, 2000 from the University of Michigan Melanoma Clinic (n = 330) were compared with the following two different sources of nonmelanoma controls: spouse/friend controls (n = 84) and healthy volunteer controls from a case-control study of psoriasis (n = 148). Using a second analytic design, comparisons between multiple primary melanoma cases (n = 62) and single primary melanoma cases (n = 330) were also evaluated to estimate odds ratios (ORs). Genotyping for the single nucleotide substitution (G to A) at position 61 in the 5' untranslated region of the EGF gene was performed from genomic DNA, and epidemiological risk factors were assessed through a telephone interview. When EGF genotypes were compared between incident primary melanoma cases and the nonmelanoma controls, the risk associated with the homozygous G/G genotype was not statistically significantly associated with an increased risk for incident primary melanoma compared with the homozygous A/A genotype [OR, 1.09; 95% confidence interval (CI); 0.65-1.85]. No strong associations with EGF G/G genotype were observed in comparisons of multiple primary and single primary melanoma cases (OR, 0.66; 95% CI; 0.25-1.73). Case subjects with tumors >/=3.5 mm compared with those <3.5 mm were not significantly associated with the G/G genotype (OR, 0.54; 95% CI; 0.12-2.35). Our data do not support a significant association between melanoma and the EGF 61*G allele or the homozygous G/G genotype. The EGF polymorphism is not a reproducible risk factor for melanoma or thick melanoma in our data. The two analytic approaches used in the study provide evidence against a strong association between EGF 61*G and melanoma and demonstrate the potential utility of case-case designs for evaluating the role of single nucleotide polymorphisms and cancer. Additional independent studies will be required to elucidate relationships between genetic variation in the EGF gene and risk of melanoma.

Influence of the renin-angiotensin system on epidermal growth factor expression in normal and cyclosporine-treated rat kidney

Epidermal growth factor (EGF) plays an important role in renal tubular regeneration after ischemic injury in kidney. The present study reports the association between the renin-angiotensin system (RAS) and EGF, and the effect of angiotensin II blockade with losartan (LSRT) on EGF expression in an experimental model of chronic cyclosporine (CsA) nephrotoxicity in rats. Two separate experiments were performed. In the first experiment, rats on the normal-salt diet (NSD; 0.3%) or low-salt diet (LSD; 0.05%) were treated with or without LSRT for four weeks. In the second experiment, rats on the NSD or LSD were given vehicle (VH group, olive oil, 1 mg/kg per day) or CsA (15 mg/kg per day) or CsA (15 mg/kg per day) plus LSRT (100 mg/L per day). Renal function, histopathology, TUNEL staining, plasma renin activity (PRA), and the expression of renin and EGF were studied. Normal rats on the LSD showed significantly increased EGF expression (cortex, 2.6-fold; medulla, 1.7-fold) and significantly decreased EGF expression with the LSRT treatment compared with the rats treated with the NSD (cortex, 74.8 vs. 10%; medulla, 22.5 vs. 5%). In contrast, the CsA-treated rats on the LSD had a significantly lower EGF expression (cortex, 98 vs. 53%; medulla, 94 vs. 14%); however, concomitant administration of LSRT increased the EGF expression (cortex, 91- vs. 3.8-fold; medulla, 19- vs. 2.4-fold) compared with the rats on the NSD. In the normal and CsA-treated LSD rats, EGF expression was well correlated with PRA. In addition, EGF expression was well correlated with the interstitial fibrosis score (r = 0.664, P < 0.01) or number of TUNEL-positive cells (r = 0.822, P < 0.01) in CsA-treated LSD rats. These results suggest that angiotensin II blockade with LSRT decreases EGF expression in normal rats on the LSD, but it protects EGF expression in CsA-induced nephrotoxicity. This finding provides a new perspective on the renoprotection of angiotensin II blockade in chronic CsA nephrotoxicity.