The process of curricular integration and its effects on anatomical knowledge retention.

INTRODUCTION: Integration has been recognized as an important aspect of medical education. After transitioning from a discipline-specific to a systems-based preclinical curriculum, we examined faculty perceptions of the integrated approach and also whether it would lead to better anatomy knowledge retention. METHODS: To understand faculty perspectives, we reviewed curricular materials, interviewed block directors, and observed educational sessions. We analyzed knowledge retention through a 27-question anatomy test, comparing scores from the last class of the discipline-based curriculum and the first two classes of the integrated curriculum. RESULTS: Planning integrated content involves purposeful ordering, is challenging for faculty, and requires additional resources. Evaluation of the integrated approach for anatomy content demonstrated a significant increase in knowledge retention (p = .012; 56.28% vs. 63.98% for old vs. new curriculum). CONCLUSIONS: This study helps the understanding of what is required for curricular integration. Our anatomy evaluation results corroborated the view that contextually embedded information is easier to learn and retain.

Using ultrasound to teach living anatomy to non-medical graduate students.

PURPOSE: Ultrasound technology is used to supplement gross anatomy instruction in many medical sciences programs. However, this technology is not common practice for anatomy instruction in nonmedical graduate-level courses. Ultrasound sessions provide a clear view of local anatomy and could help graduate students transfer anatomical content from a didactic context onto a living, moving body. This approach to instruction complements the rapidly evolving technological advances in science education and may assist with spatial understanding, knowledge retention, and student engagement. The main objective of this article was to describe the methods used to incorporate ultrasound sessions into a graduate level gross anatomy course. METHODS: The goal of the curricula was to use ultrasound technology to create a supplemental hands-on and engaging method of learning anatomy that would appeal to graduate students and possibly reinforce content. Graduate students participated in three interactive, 2-h-long ultrasound sessions that corresponded to their gross anatomy lecture material. RESULTS: Questionnaire results showed that students overwhelmingly believed that the ultrasound sessions were beneficial and that ultrasound technology should be used for anatomical instruction in graduate programs. While students found the sessions to be helpful, they sought more and longer sessions with smaller group sizes. CONCLUSION: Overall, this article describes the methods used to incorporate multimodal learning into a graduate level anatomy course and found that students supported the methods as a potentially effective and engaging way to supplement traditional gross anatomy lectures and practical laboratory sessions.

Exposure to particulate hexavalent chromium exacerbates allergic asthma pathology.

Airborne hexavalent chromate, Cr(VI), has been identified by the Environmental Protection Agency as a possible health threat in urban areas, due to the carcinogenic potential of some of its forms. Particulate chromates are produced in many different industrial settings, with high levels of aerosolized forms historically documented. Along with an increased risk of lung cancer, a high incidence of allergic asthma has been reported in workers exposed to certain inhaled particulate Cr(VI) compounds. However, a direct causal association between Cr(VI) and allergic asthma has not been established. We recently showed that inhaled particulate Cr(VI) induces an innate neutrophilic inflammatory response in BALB/c mice. In the current studies we investigated how the inflammation induced by inhaled particulate Cr(VI) might alter the pathology of an allergic asthmatic response. We used a well-established mouse model of allergic asthma. Groups of ovalbumin protein (OVA)-primed mice were challenged either with OVA alone, or with a combination of OVA and particulate zinc chromate, and various parameters associated with asthmatic responses were measured. Co-exposure to particulate Cr(VI) and OVA mediated a mixed form of asthma in which both eosinophils and neutrophils are present in airways, tissue pathology is markedly exacerbated, and airway hyperresponsiveness is significantly increased. Taken together these findings suggest that inhalation of particulate forms of Cr(VI) may augment the severity of ongoing allergic asthma, as well as alter its phenotype. Such findings may have implications for asthmatics in settings in which airborne particulate Cr(VI) compounds are present at high levels.

A cell-impermeable cyclosporine A derivative reduces pathology in a mouse model of allergic lung inflammation.

Although the main regulators of leukocyte trafficking are chemokines, another family of chemotactic agents is cyclophilins. Intracellular cyclophilins function as peptidyl-prolyl cis-trans isomerases and are targets of the immunosuppressive drug cyclosporine A (CsA). Cyclophilins can also be secreted in response to stress factors, with elevated levels of extracellular cyclophilins detected in several inflammatory diseases. Extracellular cyclophilins are known to have potent chemotactic properties, suggesting that they might contribute to inflammatory responses by recruiting leukocytes into tissues. The objective of the present study was to determine the impact of blocking cyclophilin activity using a cell-impermeable derivative of CsA to specifically target extracellular pools of cyclophilins. In this study, we show that treatment with this compound in a mouse model of allergic lung inflammation demonstrates up to 80% reduction in inflammation, directly inhibits the recruitment of Ag-specific CD4(+) T cells, and works equally well when delivered at 100-fold lower doses directly to the airways. Our findings suggest that cell-impermeable analogs of CsA can effectively reduce inflammatory responses by targeting leukocyte recruitment mediated by extracellular cyclophilins. Specifically blocking the extracellular functions of cyclophilins may provide an approach for inhibiting the recruitment of one of the principal immune regulators of allergic lung inflammation, Ag-specific CD4(+) T cells, into inflamed airways and lungs.

Blocking cyclophilins in the chronic phase of asthma reduces the persistence of leukocytes and disease reactivation.

Allergic asthma is characterized by acute influxes of proinflammatory leukocytes in response to allergen stimulation, followed by quiescent (chronic) periods between allergen challenges, during which sustained, low-level inflammation is evident. These chronic phases of disease are thought to be mediated by populations of leukocytes persisting within airways and tissues. The lack of any in situ proliferation by these cells, along with their limited lifespan, suggests that a continual recruitment of leukocytes from the circulation is needed to maintain disease chronicity. The mechanisms regulating this persistent recruitment of leukocytes are unknown. Although classic leukocyte-attracting chemokines are highly elevated after acute allergen challenge, they return to baseline levels within 24 hours, and remain close to undetectable during the chronic phase. In the present study, we investigated whether an alternative family of chemoattractants, namely, extracellular cyclophilins, might instead play a role in regulating the recruitment and persistence of leukocytes during chronic asthma, because their production is known to be more sustained during inflammatory responses. Using a new murine model of chronic allergic asthma, elevated concentrations of extracellular cyclophilin A, but not classic chemokines, were indeed detected during the chronic phase of asthma. Furthermore, blocking the activity of cyclophilins during this phase reduced the number of persisting leukocytes by up to 80%. This reduction was also associated with a significant inhibition of acute disease reactivation upon subsequent allergen challenge. These findings suggest that blocking the function of cyclophilins during the chronic phase of asthma may provide a novel therapeutic strategy for regulating disease chronicity and severity.

Syndecan-1 regulates cell migration and fibronectin fibril assembly.

Corneal scarring is a major cause of blindness worldwide and can result from the deposition of abnormal amounts of collagen fibers lacking the correct size and spacing required to produce a clear cornea. Collagen fiber formation requires a preformed fibronectin (FN) matrix. We demonstrate that the loss of syndecan1 (sdc1) in corneal stromal cells (CSC) impacts cell migration rates, the sizes and composition of focal and fibrillar adhesions, the activation of integrins, and the assembly of fibronectin into fibrils. Integrin and fibronectin expression are not altered on sdc1-null CSCs. Cell adhesion, spreading, and migration studies using low compared to high concentrations of FN and collagen I (CNI) or vitronectin (VN) with and without activation of integrins by manganese chloride show that the impact of sdc1 depletion on integrin activation varies depending on the integrin-mediated activity evaluated. Differences in FN fibrillogenesis and migration in sdc1-null CSCs are reversed by addition of manganese chloride but cell spreading differences remain. To determine if our findings on sdc1 were specific to the cornea, we compared the phenotypes of sdc1-null dermal fibroblasts with those of CSCs. We found that without sdc1, both cell types migrate faster; however, cell-type-specific differences in FN expression and its assembly into fibrils exist between these two cell types. Together, our data demonstrate that sdc1 functions to regulate integrin activity in multiple cell types. Loss of sdc1-mediated integrin function results in cell-type specific differences in matrix assembly. A better understanding of how different cell types regulate FN fibril formation via syndecans and integrins will lead to better treatments for scarring and fibrosis.

Loss of syndecan-1 is associated with malignant conversion in skin carcinogenesis.

Syndecan-1 (sdc-1) is a cell surface proteoglycan that mediates the interaction of cells with their matrix, influencing attachment, migration, and response to growth factors. In keratinocytes, loss of sdc-1 delays wound healing, reduces migration, and increases Transforming growth factor beta (TGFbeta) 1 expression. In this study we show that sdc-1 expression is significantly reduced in basal cell, squamous cell, and metastatic human skin cancers compared to normal human skin. In experimental mouse skin tumor induction, compared to wildtype (wt) BALB/c mice, papilloma formation in sdc-1 null mice was reduced by 50% and the percent of papillomas converting to squamous cell carcinoma (SCC) was enhanced. sdc-1 expression on wt mouse papillomas decreased as they converted to SCC. Furthermore, papillomas forming on sdc-1 null mice expressed suprabasal alpha3 and beta4 integrins; suprabasal beta4 integrin is a marker of a high risk for progression. While the proliferative response to phorbol-12-myristate-13-acetate (TPA) did not differ among the genotypes, sdc-1 null mice had an enhanced inflammatory response and retained higher levels of total TGFbeta1 within their skin after TPA treatment. sdc-1 null keratinocytes, transduced in vitro by oncogenic ras(Ha), expressed higher levels of beta4 integrin and had enhanced pSmad2 signaling and reduced senescence when compared to wt ras(Ha)-transduced keratinocytes. When ras(Ha)-transduced cells of both genotypes were grafted onto nude mice, null tumors converted to SCC with higher frequency confirming the skin painting experiments. These data indicate that sdc-1 is important both early in the development of skin tumors and in progression of skin cancers suggesting that reduced expression of sdc-1 could be a useful marker for progression in neoplastic skin lesions.

BALB/c and C57BL6 mouse strains vary in their ability to heal corneal epithelial debridement wounds.

Genetically engineered mice are usually produced on a mixed genetic background and can be derived from several mouse strains including 129SvJ, C57BL6, and BALB/c. To determine whether differences in recurrent corneal epithelial erosions (RCEEs), corneal epithelial stem cell deficiency (CESCD), and cell migration rate vary between two different mouse strains (BALB/c and C57BL6), 8-week mice were subjected to 1.5 (small) or 2.8mm (large) manual debridement wounds and allowed to heal for 4 weeks. Syndecan-1 (sdc-1) null mice backcrossed seven generations onto a BALB/c genetic background were also included in the RCEE and CESCD studies to permit comparisons between genotypes within a single strain. After sacrifice, corneas were assessed for the presence of recurrent erosions; no fewer than 15 corneas were used for each strain or genotype studied. Data show that the frequency of recurrent erosions after small wounds was 81+/-9% in the C57BL6 mice, 73+/-2% in the BALB/c mice, and 32+/-6% in sdc-1 null mice. Neither strain developed CESCD after small wounds. The frequency of erosions after large wounds was greater (88+/-8%) in the C57BL6 mice compared to BALB/c (60+/-2%), and sdc-1 null mice (32+/-5%). Four weeks after the large wounds, fixed, flat mounted corneas were assessed for evidence of CESCD with antibodies against the conjunctival keratin K8 and the goblet cell marker, the mucin Muc5AC. The frequency of CESCD 4 weeks after the large wounds was significantly greater in the C57BL6 mice than in the BALB/c or sdc-1 null mice. To assess cell migration rates, corneas were subjected to 1.5mm wounds and allowed to heal for 12, 15, 18, 21, and 24h. After sacrifice, corneas were stained with Richardson stain (BALB/c) or propidium iodide (C57BL6) to assess reepithelialization rates. While reepithelialization rates were similar for the early times after wounding, by 24h the C57BL6 corneas had healed faster: 16 of 30 corneas from the C57BL6 mice were closed compared to 9 of 30 of the BALB/c wounds. BALB/c corneas appeared larger overall compared to C57BL6 corneas; measurements of the overall mass of the enucleated eyes and diameters of the flat-mounted corneas confirmed that C57BL6 eyes and corneas were 6.8% and 4.4% smaller respectively than those of BALB/c mice even though the masses of the two mouse strains at 8 weeks of age were identical. Using BrdU to label dividing cells, we found that 18 h after wounding, C57BL6 and BALB/c corneal epithelia showed similar numbers of proliferating cells. To determine if the enhanced corneal epithelial cell migration rate seen in the C57BL6 mice was specific to the cornea, we conducted time-lapse studies to assess random cell migration rates in vitro using primary cultures of mouse epidermal keratinocytes. Consistent with the in vivo data, epidermal keratinocytes derived from BALB/c mice migrated 60% slower than C57BL6 cells. These data prove that strain-specific differences in cell migration rate in vivo are present in the cornea and are accompanied by differences in the frequencies of recurrent erosions and corneal epithelial stem cell deficiency.

Primary dermal fibroblasts derived from sdc-1 deficient mice migrate faster and have altered alphav integrin function.

ABSTRACT The goal of this study is to determine whether dermal fibroblasts lacking syndecan-1 (sdc1) show differences in integrin expression and function that could contribute to the delayed skin and corneal wound healing phenotypes seen in sdc-1 null mice. Using primary dermal fibroblasts, we show that after 3 days in culture no differences in alpha-smooth muscle actin were detected but sdc-1 null cells expressed significantly more alphav and beta1 integrin than wildtype (wt) cells. Transforming growth factor beta1 (TGFbeta1) treatment at day 3 increased alphav- and beta1-integrin expression in sdc-1 null cells at day 5 whereas wt cells showed increased expression only of alphav-integrin. Using time-lapse studies, we showed that the sdc-1 null fibroblasts migrate faster than wt fibroblasts, treatment with TGFbeta1 increased these migration differences, and treatment with a TGFbeta1 antagonist caused sdc-1 null fibroblasts to slow down and migrate at the same rate as untreated wt cells. Cell spreading studies on replated fibroblasts showed altered cell spreading and focal adhesion formation on vitronectin and fibronectin-coated surfaces. Additional time lapse studies with beta1- and alphav-integrin antibody antagonists, showed that wt fibroblasts expressing sdc-1 had activated integrins on their surface that impeded their migration whereas the null cells expressed alphav-containing integrins which were less adhesive and enhanced cell migration. Surface expression studies showed increased surface expression of alpha2beta1 and alpha3beta1 on the sdc-1 null fibroblasts compared with wt fibroblasts but no significant differences in surface expression of alpha5beta1, alphavbeta3, or alphavbeta5. Taken together, our data indicates that sdc-1 functions in the activation of alphav-containing integrins and support the hypothesis that impaired wound healing phenotypes seen in sdc-1 null mice could be due to integrin-mediated defects in fibroblast migration after injury.

Inflammatory bowel disease in rats: bacterial and chemical interaction.

AIM: To develop a novel model of colitis in rats, using a combination of iodoacetamide and enteropathogenic E. coli (EPEC), and to elucidate the pathophysiologic processes implicated in the development of ulcerative colitis (UC). METHODS: Male Sprague-Dawley rats (n = 158) were inoculated intrarectally on a weekly basis with 4 different combinations: (a) 1% methylcellulose (MC), (b) 100 microL of 6% iodoacetamide (IA) in 1% MC, (c) 200 microL containing 4 x 10(8) colony factor units (CFU) of EPEC, and (d) combined treatment of (IA) followed by bacteria (B) after 2 d. Thirty days post treatment, each of the four groups was divided into two subgroups; the inoculation was stopped for one subgroup and the other subgroup continued with biweekly inoculation until the end of the experiment. Colitis was evaluated by the clinical course of the disease, the macroscopic and microscopic alterations, activity of myeloperoxidase (MPO), and by TNF-alpha gene expression. RESULTS: Findings indicative of UC were seen in the combined treatment (IA + B) as well as the IA continued treatment groups: the animals showed slow rate of increase in body weight, diarrhea, bloody stools, high colonic ulcer score, as well as histological alterations characteristic of UC, with an extensive inflammatory reaction. During the course of the experiment, the MPO activity was consistently elevated and the TNF-alpha gene expression was upregulated compared to the control animals. CONCLUSION: The experimental ulcerative colitis model used in the present study resembles, to a great extent, the human disease. It is reproducible with characteristics indicative of chronicity.

Curricular response to increase recall and transfer of anatomical knowledge into the obstetrics/gynecology clerkship.

Deficits in retention of anatomy knowledge from the preclinical years to clinical application on the wards have been well documented in the medical education literature. We developed and evaluated a web and laboratory-based curriculum to address deficits in anatomy knowledge retention and to increase anatomy knowledge recall through repetition and application of clinical concepts during the obstetrics and gynecology (Ob/Gyn) core clinical clerkship. Using principles of adult learning and instructional design, a curriculum was designed consisting of (1) interactive, case-based e-modules reviewing clinically relevant anatomical topics and (2) a hands-on laboratory session reinforcing the content of the e-modules, with the practice of clinical techniques using anatomical cadaveric dissections. The curriculum's effectiveness was evaluated by using multiple choice testing and comparing baseline and final test scores. For questions testing content directly covered in this curriculum, mean final scores increased by 14.3% (P < 0.001). In contrast, for questions not directly addressed in this curriculum, mean final scores did not increase significantly, only by 6.0% (P = 0.31). Questions related to the uterus showed the greatest gains in final scores (30.3% improvement, P = 0.002). A curriculum with web-based preparatory material and a hands-on gross anatomy laboratory session effectively addresses deficits in anatomy retention and improves anatomical knowledge recall for medical students on a clinical clerkship. In the future, the authors plan to conduct a multicenter study to further evaluate the ability of this curriculum to improve clinically relevant anatomical knowledge. Anat Sci Educ 9: 337-343. © 2015 American Association of Anatomists.

Inflammatory bowel disease, colorectal cancer and type 2 diabetes mellitus: The links.

The co-occurrence of the three disease entities, inflammatory bowel disease (IBD), colorectal cancer (CRC), type 2diabetes mellitus (T2DM) along with inflammation and dismicrobism has been frequently reported. Some authors have even suggested that dysbiosis could be the link through a molecular crosstalk of multiple inflammatory loops including TGFß, NFKB, TNFα and ROS among others. This review focuses on the inflammatory process along with the role of microbiota in the pathophysiology of the three diseases. The etiology of IBD is multifactorial, and like CRC and T2DM, it is associated with a widespread and sustained GI inflammation and dismicrobism, whereby an array of pro-inflammatory mediators and other related biomolecules are up-regulated, both locally and systematically. Such a persistent or an inadequately resolved chronic inflammation may be a causative agent, in the presence other factors, leading to several pathologies such as IBD, CRC and T2DM. TGFß plays a crucial role in pancreatic ß cell malfunctioning as glucotoxicity stimulates its signaling cascade through smad 3, IL-6 and epithelial to mesenchymal transition. Such a cascade could lead to macrophages and other cells recruitment, inflammation, then IBD and CRC. NFkB is also another key regulator in the crosstalk among the pathways leading to the three disease entities. It plays a major role in linking inflammation to cancer development through its ability to up regulate several inflammatory and tumor promoting cytokines like: IL-6, IL-1 α and TNF α, as well as genes like BCL2 and BCLXL. It activates JAK/STAT signaling network via STAT3 transcription factors and promotes epithelial to mesenchymal transition. It also increases the risk for T2DM in obese people. In brief, NFKB is a matchmaker between inflammation, IBD, cancer and diabetes. In addition, TNFα plays a pivotal role in systemic inflammation. It is increased in the mucosa of IBD patients and has a central role in its pathogenesis. It also activates other signaling pathways like NFKB and MAPK leading to CRC. It is also overexpressed in the adipose tissues of obese patients thus linking it to T2DM, chronic inflammation and consequently CRC. On the other hand, increasing evidence suggests that dysbiosis plays a role in initiating, maintaining and determining the severity of IBD. Actually, among its functions, it modulates genotoxic metabolites which are able to induce CRC, a fact proven to be sustained by stool transfer from patients with CRC. Probiotics, however, may actively prevent CRC as well as IBD and results in a significant decrease in fasting glycemia in T2DM patients. In conclusion, IBD, CRC and T2DM are commonly occurring interrelated clinical problems. They share a common basis influenced by an inflammatory process, an imbalance in intestinal microbiota, and a crosstalk between various signaling pathways. Would probiotics interrupt the crosstalk or orient it in the physiological direction?

Can anatomists teach living anatomy using ultrasound as a teaching tool?

The utilization of bedside ultrasound by an increasing number of medical specialties has created the need for more ultrasound exposure and teaching in medical school. Although there is a widespread support for more vertical integration of ultrasound teaching throughout the undergraduate curriculum, little is known about whether the quality of ultrasound teaching differs if performed by anatomists or clinicians. The purpose of this study is to compare medical students' evaluation of ultrasound anatomy teaching by clinicians and anatomists. Hands-on interactive ultrasound sessions were scheduled as part of the gross anatomy course following principles of adult learning and instructional design. Seven teachers (three anatomists and four clinicians) taught in each session. Before each session, anatomists were trained in ultrasound by clinicians. Students were divided into groups, rotated teachers between sessions, and completed evaluations. Results indicated students perceived the two groups as comparable for all factors except for knowledge organization and the helpfulness of ultrasound for understanding anatomy (P < 0.001). However, results from unpaired samples t-tests demonstrated a nonstatistically significant difference between the groups within each session for both questions. Moreover, students' test performance for both groups was similar. This study demonstrated that anatomists can teach living anatomy using ultrasound with minimal training as well as clinicians, and encourage the teaching of living anatomy by anatomists in human anatomy courses using ultrasound. Repeating this study at a multicenter level is currently being considered to further validate our conclusion.

Anatomical knowledge retention in third-year medical students prior to obstetrics and gynecology and surgery rotations.

Surgical anatomy is taught early in medical school training. The literature shows that many physicians, especially surgical specialists, think that anatomical knowledge of medical students is inadequate and nesting of anatomical sciences later in the clinical curriculum may be necessary. Quantitative data concerning this perception of an anatomical knowledge deficit are lacking, as are specifics as to what content should be reinforced. This study identifies baseline areas of strength and weakness in the surgical anatomy knowledge of medical students entering surgical rotations. Third-year medical students completed a 20-25-question test at the beginning of the General Surgery and Obstetrics and Gynecology rotations. Knowledge of inguinal anatomy (45.3%), orientation in abdominal cavity (38.8%), colon (27.7%), and esophageal varices (12.8%) was poor. The numbers in parentheses are the percentage of questions answered correctly per topic. In comparing those scores to matched test items from this cohort as first-year students in the anatomy course, the drop in retention overall was very significant (P = 0.009) from 86.9 to 51.5%. Students also scored lower in questions relating to pelvic organs (46.7%), urogenital development (54.0%), pulmonary development (17.8%), and pregnancy (17.8%). These data showed that indeed, knowledge of surgical anatomy is poor for medical students entering surgical clerkships. These data collected will be utilized to create interactive learning modules, aimed at improving clinically relevant anatomical knowledge retention. These modules, which will be available to students during their inpatient surgical rotations, connect basic anatomy principles to clinical cases, with the ultimate goal of closing the anatomical knowledge gap.

Design for learning: adapting the microscopic anatomy laboratory to adult learners.

Medical school curricula are undergoing transformational change in response to calls for integrating content across courses and years to enable better retention and application and for individualizing learning to meet the diverse backgrounds and thus differing needs of students. To address the related teaching challenges, faculty can employ solid principles of adult learning and instructional design and use teaching strategies that stimulate different learning styles. We developed laboratory sessions that follow a learner-centered instructional design model we refer to as "PLHET," reflecting the steps of preparing, linking, hooking, engaging, and transferring learning, and also applied teaching strategies that reflect Kolb's four styles of learning (accommodative, divergent, assimilative, and convergent). We utilized a group learning format to promote active learning, teamwork, and self-direction. Preliminary data based on student surveys of laboratory activity show positive responses. In the future, we will test the hypothesis that this design will improve medical students' performance.

Reduced migration, altered matrix and enhanced TGFbeta1 signaling are signatures of mouse keratinocytes lacking Sdc1.

We have reported previously that syndecan-1 (Sdc1)-null mice show delayed re-epithelialization after skin and corneal wounding. Here, we show that primary keratinocytes obtained from Sdc1-null mice and grown for 3-5 days in culture are more proliferative, more adherent and migrate more slowly than wt keratinocytes. However, the migration rates of Sdc1-null keratinocytes can be restored to wild-type levels by replating Sdc1-null keratinocytes onto tissue culture plates coated with fibronectin and collagen I, laminin (LN)-332 or onto the matrices produced by wild-type cells. Migration rates can also be restored by treating Sdc1-null keratinocytes with antibodies that block alpha6 or alphav integrin function, or with TGFbeta1. Antagonizing either beta1 integrin function using a function-blocking antibody or TGFbeta1 using a neutralizing antibody reduced wild-type keratinocyte migration more than Sdc1-null keratinocyte migration. Cultures of Sdc1-null keratinocytes accumulated less collagen than wild-type cultures but their matrices contained the same amount of LN-332. The Sdc1-null keratinocytes expressed similar total amounts of eight different integrin subunits but showed increased surface expression of alphavbeta6, alphavbeta8, and alpha6beta4 integrins compared with wild-type keratinocytes. Whereas wild-type keratinocytes increased their surface expression of alpha2beta1, alphavbeta6, alphavbeta8, and alpha6beta4 after treatment with TGFbeta1, Sdc1-null keratinocytes did not. Additional data from a dual-reporter assay and quantification of phosphorylated Smad2 show that TGFbeta1 signaling is constitutively elevated in Sdc1-null keratinocytes. Thus, our results identify TGFbeta1 signaling and Sdc1 expression as important factors regulating integrin surface expression, activity and migration in keratinocyte and provide new insight into the functions regulated by Sdc1.