Biomedical subjects

Choun-Ki Joo

Publications and source records attributed to Choun-Ki Joo.

At least 19 recordsLinked to original sources

PubMed2006

Transactivation of EGFR mediates insulin-stimulated ERK1/2 activation and enhanced cell migration in human corneal epithelial cells.

PURPOSE: Insulin activates phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK)-1/2 in human corneal epithelial cells. These events have been shown to be involved in wound healing. However, the mechanism of insulin-induced ERK pathway is not clear during corneal wound healing. In this study, the effect of insulin associated with epidermal growth factor receptor (EGFR) on wound healing in transformed human corneal epithelial cells was investigated to determine the signaling mechanism involved. METHODS: SV40-immortalized human corneal epithelial (THCE) cells were cultured on a diluted Matrigel matrix that resembled the basement membrane of the corneal epithelium. A wound was introduced with a micropipette tip, and closure of the scratch wound was photographed 12 h after exposure to insulin. Activation of EGFR was analyzed by immunoprecipitation, and cytoskeletal rearrangements were visualized with rhodamine-conjugated phalloidin. RESULTS: Exposure of corneal epithelial cells to insulin induced phosphorylation of EGFR. Inhibition of EGFR activation by AG1478 or the MMP inhibitor, GM6001, reduced phosphorylation of insulin-induced ERK in the presence of insulin and delayed wound closure. In addition, cells exposed to insulin contained stress fibers and their submembranous cortical actin was depleted. These effects were inhibited by AG1478. CONCLUSIONS: Inhibition of EGFR activity decreases cell migration involved in insulin-induced wound repair, an effect that mimics inhibition of MMP activation. Inhibition of MMP activity leads to decreased EGFR phosphorylation. Our data show that insulin stimulates wound healing in the corneal epithelium by activating EGFR, and point to a novel insulin signaling pathway that acts during corneal wound healing.

Cell Line, Transformed↗

PubMed2006

Inhibition of nNOS and COX-2 expression by lutein in acute retinal ischemia.

OBJECTIVE: Lutein is a major nutrient in the retina. Lutein has an antioxidative effect and protects against macular degeneration and retinal degenerative disease. However, the mechanism of lutein is not clear in retinal degeneration, and a role for lutein is not known in ischemic injury. In this study, an ischemia-induced rat retina was examined to determine the effect of the lutein on ischemic retinal cell death. METHODS: We used a transient ischemia model of high intraocular pressure in the rat. Lutein (Kemin Foods, LC) was injected into the intraperitoneal or intravitreous before ischemia. Retinal degeneration was observed by light microscopy 24 h after ischemia. Expressions of neuronal nitric oxide synthase (nNOS) and cyclo-oxygenase-2 (COX-2) were detected by western blot analysis at various times after retinal ischemia. RESULTS: The nNOS and COX-2 expression levels were increased early in ischemic control retinas, but these increases were inhibited by lutein. In addition, the inhibitory effect of lutein was observed to be dose dependent. Further, ischemia-induced cell death was inhibited by lutein. Lutein-injected ischemic retina appeared similar to normal retina. CONCLUSION: This study investigated the protective effect of lutein on retinal ischemia and the inhibitory effect of nNOS and COX-2 expressions. These results suggest that a supplement with lutein may have the potential to inhibit ischemic cell death by this mechanism in the neural retina.

Acute Disease↗

PubMed2006

Inhibition of cyclooxygenase-2 expression by zinc-chelator in retinal ischemia.

The zinc ion (Zn2+) is abundant in neurons. However, excessive Zn2+ can induce neuronal cell death. This study examined the role of Zn2+ in transient retinal ischemia in adult male rats. The rats were sacrificed 4-24 h after retinal ischemia by high intra-ocular pressure, and the retinas were prepared for microscopic examination of retinal cell degeneration, and fluorescence microscopy using zinquin ethyl ester as the zinc ion-specific probe. Moreover, COX-2 expression was observed by Western blotting. In control retinas, there was a low Zn2+ concentration in the inner plexiform layer (IPL), a high Zn2+ concentration in the outer plexiform layer (OPL), and no detectable Zn2+ in either the ganglion cell layer (GCL) or the inner nuclear layer (INL). In contrast, in the retinas exposed to ischemia without the administration of the zinc ion chelators (Ca2+-EDTA and TPEN), Zn2+ deposits were found in the IPL and INL beginning 4 h after ischemia and degeneration of neurons was found in the GCL and INL. Less Zn2+ accumulation in the IPL and INL and less neuronal degeneration in the GCL and INL were found in the retinas treated with Ca2+-EDTA or TPEN before ischemia. Furthermore, the COX-2 protein levels increased 4-8 h after retinal ischemia, and chelation of zinc ion inhibited this effect. These results suggest that the accumulation of Zn2+ following an ischemic insult can cause retinal degeneration and induce abnormal COX-2 expression.

Animals↗

PubMed2006

Corneal ectasia after PRK: clinicopathologic case report.

PURPOSE: To describe the clinical and ultrastructural features of a prominent ectasia of the cornea that occurred 9 years after excimer laser photorefractive keratectomy (PRK). METHODS: Analysis of corneal topography and ultrastructural examination by transmission electron microscopy (TEM) were used to assess the ectatic cornea. RESULTS: The intended laser ablation in the left eye was 74 microm, and the preoperative ultrasonic pachymetry was 536 microm. Orbscan II (V 3.00; Orbtek, Salt Lake City, UT) observations revealed inferior topographic steepening and protrusion of the anterior and posterior corneal surfaces 13 years after the patient underwent PRK. The least thickness of the cornea was 456 microm. TEM showed that the epithelial basement membrane had degenerated into subepithelial stroma, and apoptotic keratocytes with cell debris on the extracellular matrix were observed in the stroma. However, the endothelial cells were normal. CONCLUSION: Clinical examination of an eye that had developed corneal ectasia 9 years after PRK showed forward protrusion of both anterior and posterior corneal surfaces. Ultrastructural examination also revealed a degenerated stroma. However, there was no abnormality of the corneal endothelium.

Adult↗

PubMed2006

Expression of Wnt and MMP in epithelial cells during corneal wound healing.

PURPOSE: To study the expression of Wnt during corneal wound healing and to understand the signaling mechanism involved. METHODS: Rat cornea was demarcated on the central area by 4-mm trepine, and the epithelium within this area was removed by scalpel. The epithelium was scraped and isolated to extract RNA. To determine the proliferation of corneal epithelial cells, corneoscleral rims from human donors were treated with dispase II for 15 minutes, and epithelial cells were isolated. Cells were plated on a 3T3 feeder cells layer. The proliferation of corneal epithelial cells was evaluated by colony-forming efficiency. RESULTS: Wnt 5b and 7a were rapidly induced in wounded cornea, and Wnt 7a promoted proliferation of corneal epithelial cells. In addition, matrix metalloproteinase (MMP)-12 was expressed in wounded rat corneal epithelium. Transcription of MMP-12 was responsive to Wnt/beta-catenin signaling. Function blockade of MMP-12 delayed Wnt 7a-induced cell proliferation. CONCLUSION: These results indicate that Wnt proteins and MMP-12 regulate the proliferation of corneal epithelial cells and that Wnt signaling contributes to the resurfacing of defective areas during corneal wound healing.

Animals↗

PubMed2006

Comparison of forward shift of posterior corneal surface after operation between LASIK and LASEK.

PURPOSE: To compare the forward shift of the posterior corneal surface as a function of time after surgery between successful laser in situ keratomileusis (LASIK) and laser-assisted subepithelial keratectomy (LASEK). METHODS: Twenty-two eyes from 14 patients who underwent LASIK and 19 eyes from 10 patients who underwent LASEK were reviewed retrospectively. The uncorrected visual acuity, spherical equivalent and pachymetry were obtained before and 1 or 2 weeks and 2, 6, 12, and 24 months after surgery. The change in the elevation of the posterior corneal surface was assessed using the difference map of an Orbscan II (Bausch and Lomb, Salt Lake City, Utah, USA), which was generated from the preoperative and subsequent postoperative elevation map. RESULTS: One or 2 weeks after LASIK and LASEK, the posterior corneal surface had shifted forward by 18.00 and 25.90 microm, respectively (p = 0.008). However, the mean posterior corneal surface reduced by 3.05 microm from 1 or 2 weeks to 2 years in the LASIK group (p = 0.359). In contrast, the mean posterior corneal surface had reduced by 12.40 microm in the LASEK group (p = 0.004). This forward shift did not return to the corneal normal elevation observed prior to surgery in the two groups. CONCLUSIONS: Refractive surgery induced a forward shift of the posterior corneal surface early postoperatively in the LASIK and LASEK groups, and this change after LASEK was significantly larger than that observed after LASIK. The posterior corneal surface gradually shifted backwards depending on the time course in both groups, but they did not return to the preoperative levels.

Adult↗

PubMed2006

Keratectasia after laser in situ keratomileusis. Clinicopathological case report.

PURPOSE: To describe the morphological features of a prominent ectasia of the cornea after laser in situ keratomileusis (LASIK). METHODS: The morphology of the ectatic corneas was examined using corneal topography, light microscopy and transmission electron microscopy in 2 cases who underwent penetrating keratoplasty due to poor visual acuity induced by progressive corneal ectasia after LASIK. RESULTS: On topographic examination, the apex of the corneal surface was observed within the central 3-mm zone, and the smallest thickness was 0.116 and 0.271 mm in each case. On histological examination, the epithelial layer became thinner and detached easily. Bowman's membrane was broken down and folded. An irregular arrangement of the stromal lamellae with fibroblastic keratocytes was found. The fulled fiber cell, a transformed epithelial cell, was visible in a plane on Bowman's layer in the central region. In contrast, the corneal endothelium was intact, and no abnormality was found in both cases. CONCLUSION: On morphological examination of 2 cases with corneal ectasia, a forward protrusion of both the anterior and posterior corneal surfaces occurred, and epithelial detachment, Bowman's membrane breakage and folding and irregular lamellae were found. The 2 cases had greatly thinned and protruding corneas, yet there was no abnormality in the corneal endothelium.

Adult↗

PubMed2006

The side population cells in the rabbit limbus sensitively increased in response to the central cornea wounding.

PURPOSE: Side population (SP) cells are known to reside in the limbus as putative corneal epithelial stem cells. This study was performed to demonstrate the presence and the characteristics of SP cells in the rabbit limbal epithelium and explore their sensitivity in response to the central cornea wounding. METHODS: To sort out the SP cells, freshly isolated rabbit limbal and central corneal epithelial cells were subjected to Hoechst 33342 dye efflux assay. For characterization of the sorted SP cells, RT-PCR analysis, semi-dry three-dimensional (3-D) cell culture, and transplantation in nude mice were performed. To explore wound sensitivity of the limbal SP cells, the rabbit central cornea was wounded by direct contact of a 6-mm paper disk soaked with 1 N NaOH, and changes in the population size of the SP cells and the colony-forming efficiency (CFE) was monitored on days 1, 2, and 5 after wounding. RESULTS: The SP cells were present in the rabbit limbal epithelium with an incidence of 0.73% +/- 0.14% (n = 8) and were smaller in cell size than the major population (MP) cells, quiescent in the cell cycle, and in the undifferentiated state. The SP cells were able to regenerate the cornea-like structure with basal enrichment of p63-positive cells by in vitro 3-D culture and in vivo transplantation, all of which were best achieved by the whole population (WP) of cells comprising SP and MP cells. After central cornea wounding, this rare population of the limbal SP cells increased in size fivefold on day 1 and then decreased on day 2. The transient increase in the SP cells was subsequently followed by the propagation of an increase in CFE in the limbal MP cells on day 2 and then in the corneal MP cells on day 5. In the hematopoietic colony-forming assay, the limbal SP cells gave approximately eightfold higher CFU than the limbal MP cells. CONCLUSIONS: The SP cells identified in the rabbit limbus are an undifferentiated and noncycling rare epithelial cell population, which sensitively respond to the central cornea wounding by their transient increase in the population size.

Animals↗

PubMed2005

Induction of p21Cip1-mediated G2/M arrest in H2O2-treated lens epithelial cells.

PURPOSE: Oxidative damage is one of the major factors associated with the formation of age-related cataract and with senescence of various cell types. Although the effects of oxidative stress are complex, we focused on whether oxidative damage affects control of the cell cycle in lens epithelial cells. METHODS: BrdU labeling and FACS analysis were used to investigate the effect of H2O2 on the cell cycle of HLE B-3 cells. In addition, western and Northern blot analysis were performed to assess the expression of cell cycle regulatory proteins and transfection with siRNA was used to knock out expression of p21Cip1. The activation of MAPK family members by oxidative stress was assessed using antibodies to detect the activated forms. To confirm the effect of H2O2 on an ex vivo model, its effect on cultures of the lenses of 3-week-old SD rats were examined. The localization and expression of PCNA and p21Cip1 in the rat lenses were analyzed by immunohistochemistry. RESULTS: FACS analysis showed that H2O2 treatment induced G2/M phase arrest of HLE B-3 cells. p21Cip1 was strongly induced by H2O2, whereas expression of other cell cycle genes was unchanged. Attenuation of p21Cip1 expression using siRNA reduced the H2O2 induced G2/M arrest. Furthermore, JNK and ERK were activated by H2O2 and their specific inhibitors SP600125 (for JNK) and U0126 (for ERK1/2) prevented p21Cip1 expression and blocked cell cycle arrest. H2O2 treatment of a rat lens organ culture also caused an increase in p21Cip1. However, H2O2 treatment lowered the levels of p27Kip1, cdc2, and PCNA in the rat lens culture, unlike in the HLE B-3 cells. CONCLUSIONS: The accumulation of p21Cip1 in lenses exposed to oxidative stress may play a role as a defensive mediator of oxidative damage, an indicator for senescence or aging, or an inducer for the formation of cataract. This finding links oxidative stress with p21Cip1-mediated control of the cell cycle in lens epithelial cells.

Animals↗

PubMed2005

Wnt-7a up-regulates matrix metalloproteinase-12 expression and promotes cell proliferation in corneal epithelial cells during wound healing.

Corneal wound repair involves the rapid coverage of a denuded area by residual epithelial cells. During wound healing, there are different cell behaviors in different regions of the epithelium: cell proliferation in the peripheral epithelium and cell migration in the central epithelium. We found that Wnt-7a was rapidly induced in the wounded cornea, promoted the proliferation of corneal epithelial cells, and enhanced wound closure. Matrix metalloproteinase-12 (MMP-12) was detected in the peripheral epithelium, where cell proliferation was enhanced, but was diminished in the migrating central epithelium. Wnt-7a induced the accumulation of beta-catenin and the activation of Rac and beta-catenin, and Rac synergistically induced the transcription of MMP-12. Blocking the function of MMP-12 delayed wound closure induced by Wnt-7a. Our results also suggest that, in addition to the beta-catenin pathway, Wnt-7a might induce a beta-catenin-independent pathway. By regulating the proliferation of corneal epithelial cells, Wnt-7a and MMP-12 appear to contribute to corneal wound healing.

Animals↗

PubMed2005

Translocation of nuclear factor-kappaB on corneal epithelial cells induced by ultraviolet B irradiation.

PURPOSE: This study was performed to elucidate the role of nuclear factor-kappaB (NF-kappaB) in the death of corneal epithelial cells after ultraviolet (UV) irradiation. METHODS: Simian virus 40-transfected human corneal epithelial cells (T-HCECs) were used in this study. Cell cultures were irradiated with a UVB (312 nm) source located 10 cm from the bottom of the slides for 10, 20, 30, or 40 s. Cytotoxicity was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Translocation of NF-kappaB was examined by immunocytochemistry using anti-NF-kappaB p65 antibody and electrophoretic mobility shift assay (EMSA). Sulfasalazine and SN-50, specific NF-kappaB inhibitors, were used to confirm the role of NF-kappaB by pretreating samples for 30 min before UV irradiation, after which cytotoxicity and NF-kappaB translocation were evaluated. RESULTS: When T-HCECs were irradiated with UVB, translocation of NF-kappaB was observed with immunocytochemistry. These translocations peaked 2 h after UV irradiation during EMSA. When pretreated with sulfasalazine or SN-50, the translocation of NF-kappaB was blocked. Cellular death after UV irradiation was also markedly blocked by sulfasalazine. CONCLUSION: These findings suggest that NF-kappaB plays an important role in cellular death after UV irradiation.

Cell Line, Transformed↗

PubMed2005

Cellular death mediated by nuclear factor kappa B (NF-kappaB) translocation in cultured human lens epithelial cells after ultraviolet-B irradiation.

PURPOSE: To determine the role of nuclear factor kappa B (NF-kappaB) in the death of lens epithelial cells (LECs) after ultraviolet (UV) irradiation. SETTING: Department of Ophthalmology, Ilsan Paik Hospital, Inje University, Korea. METHODS: Cultures of simian virus 40 transfected human LECs (HLE B-3 cells) were were irradiated with a UVB source (312 nm) located 10 cm from the bottom of the slides for 1, 2, 3, or 4 minutes. Cytotoxicity was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. Translocation of NF-kappaB was examined by immunocytochemistry using anti-NF-kappaB p65 antibody and electrophoretic mobility shift assay (EMSA). Sulfasalazine, a specific NF-kappaB inhibitor, was used to confirm the role of NF-kappaB by pretreating samples for 30 minutes before UV irradiation, after which cytotoxicity and NF-kappaB translocation were evaluated. RESULTS: When HLE B-3 cells were irradiated with UVB, translocation of NF-kappaB was observed with immunocytochemistry. These translocations peaked during EMSA 6 hours after UV irradiation. In HLE B-3 cells pretreated with sulfasalazine, the translocation of NF-kappaB was blocked. Cellular death after UV irradiation was also markedly reduced by sulfasalazine pretreatment. Ultraviolet irradiation can translocate NF-kappaB, and sulfasalazine is a useful blocking agent in this pathway. In this experimental model, sulfasalazine prevented cellular death after UV irradiation. CONCLUSION: The findings suggest that NF-kappaB plays an important role in cellular death after UV irradiation.

Apoptosis↗

PubMed2005

The effect of capsular tension ring on posterior capsular opacity in cataract surgery.

This study was performed to evaluate the efficacy and safety of the capsular tension ring on posterior capsular opacity in comparison with cases undergoing intraocular lens (IOL) implantation alone. We analyzed 127 eyes which had undergone cataract surgery, including capsular tension ring insertion, along with 127 eyes which had undergone IOL implantation alone by the same surgeon from September 1998 to March 2003. In the insertion group, 41 eyes (group A) had been followed up for more than one year after silicone IOL implantation, as had 40 eyes (group B) in the control group. We compared the incidence, type, and degree of capsular opacity between A and B groups and also endothelial cell loss after surgery between the two groups. For insertion group A, the frequency of posterior capsular opacity was lower(7.3%), the duration to development was longer, and the energy required for Nd-Yag capsulotomy of PCO was less than for control group B (25%) (p=0.037). The endothelial cell count loss rate was not significantly different between the two groups (p=0.522). The capsular tension ring is associated with a significantly reduced incidence of posterior capsular opacity and is a safe procedure.

Adult↗

PubMed2005

Visual quality after wavefront-guided LASIK for myopia.

This study evaluated the visual quality after wavefront-guided laser in situ keratomileusis (LASIK) for treating myopia. Thirty-two eyes with moderate myopia (-5.78 - -2.17D) and 25 eyes with high myopia (-7.78 - -6.17D) were prospectively reviewed. The contrast sensitivity (CS), glare and the total higher order aberrations (HOA) were measured before and 1 week, 1 month and 2 months after LASIK. The pupil diameter was measured at day- and night-time illumination. The CS and glare at all spatial frequencies were not reduced after wavefront-guided LASIK (p<0.05) and the difference between the moderate and high myopia group was not significant. No significant correlation was found between the amounts of myopia and the postoperative CS (p>0.05). The area under the log contrast sensitivity function (AULCSF) showed no correlation with the total HOA (r2=-0.071, p=0.612, between the daytime AULCSF and the total HOA with a 4 mm entrance pupil, r2=-0.176, p=0.260, between the nighttime AULCSF and the total HOA with a 6 mm entrance pupil). There was no decrease in CS and glare after wavefront-guided LASIK for myopia. In conclusion, wavefront-guided LASIK based on the individual ablation patterns is a good option for refractive surgery to improve the visual quality in both moderate and high myopia cases.

Adult↗

PubMed2004

Adenomatous polyposis coli is down-regulated by the ubiquitin-proteasome pathway in a process facilitated by Axin.

Adenomatous polyposis coli (APC) protein and Axin form a complex that mediates the down-regulation of beta-catenin, a key effector of Wnt signaling. Truncation mutations in APC are responsible for familial and sporadic colorectal tumors due to failure in the down-regulation of beta-catenin. While the regulation of beta-catenin by APC has been extensively studied, the regulation of APC itself has received little attention. Here we show that the level of APC is down-regulated by the ubiquitin-proteasome pathway and that Wnt signaling inhibits the process. The domain responsible for the down-regulation and direct ubiquitination was identified. We also show an unexpected role for Axin in facilitating the ubiquitination-proteasome-mediated down-regulation of APC through the oligomerization of Axin. Our results suggest a new mechanism for the regulation of APC by Axin and Wnt signaling.

Adenomatous Polyposis Coli Protein↗

PubMed2004

Transdifferentiation of cultured bovine lens epithelial cells into myofibroblast-like cells by serum modulation.

An after-cataract is caused by the proliferation of residual cells over the equator of the lens. These cells subsequently migrate to the posterior lens capsule, where they undergo aberrant differentiation into fiber-like cells or transdifferentiation into fibroblast-like cells. To study the precise molecular mechanisms of transdifferentiation, an attempt was made to establish an in vitro system, in which the lens epithelial cells (LECs) of the pre-equatorial zone could be transdifferentiated into fibroblast-like cells. The required conditions for culturing the LECs were identified as consisting of four phases; intact bovine explants, explant-cultured, serum-modulated and additionally modulated LECs. The LECs of each phase were compared by examining changes in the expression of the epithelial-mesenchymal transition (EMT)-related genes and changes in cellular morphology and adhesion. The explants that were cultured in a medium containing 10% fetal bovine serum (FBS) for 2 weeks, showed changes in the expression of the EMT-related genes, although the other explant-cultured cells maintained an epithelial morphology. To introduce a transition into mesenchymal cells, the explant cultures were subcultured in a medium containing 20% FBS for six passages. These cells displayed an elongated morphology and were able to grow and migrate in a similar way to fibroblast cells. The expression of the EMT-related genes, such as, extracellular matrix proteins and integrins, was altered. This was similar to the alteration of the 3-dimensional collagen gels model previously reported. During a further process of EMT by additional serum modulation, the inhibitory effect of disintegrin on cell adhesion was gradually decreased, integrin expression was differentially regulated and alpha-smooth muscle actin was post-translationally modified from the point of passage number six. Overall, it can be concluded that terminal transdifferentiation accompanies changes in the cytoskeletal proteins and cell surface molecules. These are modulated in systematic patterns of post-transcriptional and post-translational regulation and patterns of gene regulation, by the synergic effects of several transforming factors contained in serum. Therefore, posterior capsular opacification may also be accompanied by this molecular mechanism.

Animals↗

PubMed2004

Possible role of amyloid beta-(1-40)-BSA conjugates in transdifferentiation of lens epithelial cells.

We investigated whether amyloid beta(Abeta) aggregates have transforming growth factor beta- like cytokine activity and cause transdifferentiation of lens epithelial cells, leading to certain types of cataract. In order to mimic Abetaaggregates, Abeta-(1-40) was crosslinked to bovine serum albumin (BSA) with disuccinimidyl suberate according to a previously described procedure. When human lens epithelial B-3 (HLE B-3) cells were treated with the Abeta-(1-40)-BSA conjugates, we observed the translocation of Smad-3, as well as the induced mRNA levels of fibronectin (FN), collagen type I (Col I), smooth muscle actin (SMA) and matrix metalloproteinase-2 (MMP-2). In addition, we investigated the morphology of rat whole lens cultured for 5 days in the presence of Abeta-(1-40)-BSA, and the immunohistochemical localizations of Abeta-(1-40)/amyloid precursor protein (APP) in human clinical tissues beneath the anterior capsules. In rat whole lens cultures, treatment with Abeta-(1-40)-BSA produced a transformed morphology that had multiple layers of lens epithelial cells. To compare the anterior capsules in anterior subcapsular cataracts with those in nuclear cataracts, immunohistochemical studies of Abeta/APP in human clinical tissues revealed that the predominant immunostaining of Abeta occurs in the anterior epithelial plaques, which likely produces the abnormal extracellular matrix. Thus, these findings suggest that Abeta aggregates in vivo are possibly involved in the regulatory process by which lens epithelial cells may transdifferentiate into fibroblast-like cells, as well as help understand the mechanisms which lead to certain types of cataractogenesis.

Amyloid beta-Peptides↗

PubMed2004

Integrin-linked kinase function is required for transforming growth factor beta-mediated epithelial to mesenchymal transition.

The role of integrin-linked kinase (ILK) in transforming growth factor beta (TGFbeta)-mediated epithelial to mesenchymal transition was investigated. A stable transfection of dominant-negative ILK results in the prevention of TGFbeta-mediated E-cadherin delocalization. TGFbeta-mediated phosphorylation of Akt at Ser-473 was inhibited by dominant-negative ILK and PI3K inhibitors, LY294002 and wortmannin. Treatment with TGFbeta stimulated induction of Akt and ILK kinase activity in HaCat control cells. This increased ILK activity by TGFbeta was lowered by PI3K inhibitor, LY294002. In addition, PI3K inhibitor, dominant-negative Akt, and dominant-negative ILK could not block TGFbeta-mediated C-terminal phosphorylation of Smad2. Taken together, these data suggest that PI3K-ILK-Akt pathway that is independent of the TGFbeta-induced Smad pathway is required for TGFbeta-mediated epithelial to mesenchymal transition.

Cell Differentiation↗