ABSTRACT
BACKGROUND: Adolescents (10-19 years) are a big segment of the Nigerian population, and they face serious risks to their health and well-being. Maternal mortality is very high in Nigeria, and rates of pregnancy and maternal deaths are high among female adolescents. Rates of HIV infection are rising among adolescents, gender violence and sexual abuse are common, and knowledge about sexual and reproductive health risks is low. Adolescent sexual and reproductive health (ASRH) indicators are worse in the north of the country. OBJECTIVE: In Bauchi State, northern Nigeria, the project will document the nature and extent of ASRH outcomes and risks, discuss the findings and codesign solutions with local stakeholders, and measure the short-term impact of the discussions and proposed solutions. METHODS: The participatory research project is a sequential mixed-methods codesign of a pragmatic cluster randomized controlled trial. Focus groups of local stakeholders (female and male adolescents, parents, traditional and religious leaders, service providers, and planners) will identify local priority ASRH concerns. The same stakeholder groups will map their knowledge of factors causing these concerns using the fuzzy cognitive mapping (FCM) technique. Findings from the maps and a scoping review will inform the contextualization of survey instruments to collect information about ASRH from female and male adolescents and parents in households and from local service providers. The survey will take place in 60 Bauchi communities. Adolescents will cocreate materials to share the findings from the maps and survey. In 30 communities, randomly allocated, the project will engage adolescents and other stakeholders in households, communities, and services to discuss the evidence and to design and implement culturally acceptable actions to improve ASRH. A follow-up survey in communities with and without the intervention will measure the short-term impact of these discussions and actions. We will also evaluate the intervention process and use narrative techniques to assess its impact qualitatively. RESULTS: Focus groups to explore ASRH concerns of stakeholders began in October 2021. Baseline data collection in the household survey is expected to take place in mid-2022. The study was approved by the Bauchi State Health Research Ethics Committee, approval number NREC/03/11/19B/2021/03 (March 1, 2021), and by the Faculty of Medicine and Health Sciences Institutional Review Board McGill University (September 13, 2021). CONCLUSIONS: Evidence about factors related to ASRH outcomes in Nigeria and implementation and testing of a dialogic intervention to improve these outcomes will fill a gap in the literature. The project will document and test the effectiveness of a participatory approach to ASRH intervention research. TRIAL REGISTRATION: ISRCTN Registry ISRCTN18295275; https://www.isrctn.com/ISRCTN18295275. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36060.
ABSTRACT
BACKGROUND: Digital stories-first-person, self-made, 2- to 3-minute videos-generate awareness, impart knowledge, and promote understanding on topics such as mental illness. Digital stories are a narrative-based art form often created by individuals without formal training in filmmaking to relate personal experiences. Somewhat like digital narratives, video testimonies created within the social marketing or fundraising campaigns of government agencies and private or public corporations aim to reduce the stigma of mental illness while supporting research and services. In video testimonies, personal stories are captured on camera by professional filmmakers. Sharing critical life events greatly benefits tellers and listeners alike, supporting catharsis, healing, connectiveness, and citizenship. OBJECTIVE: This study explores digital stories and video testimonies featuring mental illness and recovery in their ability to elicit empathy and compassion while reducing stigma among viewers. METHODS: Using mixed methods, phase 1 will involve a search of Canadian social marketing activities and fundraising campaigns concerning mental illness and recovery. Phase 2 will involve the organization of digital storytelling workshops in which participants will create digital stories about their own experiences of mental illness and recovery. In phase 3, a pilot randomized controlled trial will be undertaken to compare marketing and fundraising campaigns with digital stories for their impact on viewers, whereas phase 4 will focus on knowledge dissemination. RESULTS: Ethics approval for this study was received in March 2021. Data on the feasibility of the study design and the results of the controlled trial will be generated. This study will produce new knowledge on effective ways of promoting mental health awareness and decreasing stigma, with practical importance for future social marketing and fundraising campaigns. The anticipated time for completion within the 2-year study period includes 9 months for phase 1 (knowledge synthesis activities identifying social marketing and fundraising campaigns) and phase 2 (storytelling workshops), 11 months for phase 3 (feasibility assessment and data collection: randomized controlled trial), and 2 months for phase 4 (knowledge dissemination). CONCLUSIONS: The knowledge generated will have practical implications for the public and for future social marketing and fundraising campaigns promoted by government agencies as well as nonprofit and for-profit organizations by enhancing our understanding of how individuals and societies respond to stories of mental distress and what prompts citizens to help others. TRIAL REGISTRATION: ClinicalTrials.gov NCT04881084; https://clinicaltrials.gov/ct2/show/NCT04881084. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/33525.
ABSTRACT
BACKGROUND: Malaria is a leading cause of morbidity and mortality among children under 5 years in Malawi, and especially among those from rural areas of central Malawi. The goal of this study was to examine the prevalence and determinants of malaria infection among children in rural areas of Dowa district in central Malawi. METHODS: A multistage, cross-sectional study design was used to systematically sample 523 child-mother dyads from postnatal clinics. A survey was administered to mothers and a rapid malaria infection diagnostic test was administered to children. The main outcome was positive malaria diagnostic tests in children. Logistic regressions were used to determine risk factors associated with malaria among children aged 2 to 59 months. RESULTS: The prevalence of malaria among children under 5 years was 35.4%. Results suggest that children of mothers who experienced recent intimate partner violence (IPV) were more likely to be diagnosed with malaria (AOR: 1.88, 95% CI 1.19-2.97; P = 0.007) than children of mothers who did not. Children of mothers who had no formal education were more likely to be diagnosed with malaria (AOR: 2.77, 95% CI 1.24-6.19; P = 0.013) than children of mothers who had received secondary education. Children aged 2 to 5 months and 6 to 11 months were less likely to be diagnosed with malaria (AOR: 0.21, 95% CI 0.10-0.46; P = 0.000 and AOR: 0.43; 95% CI 0.22-0.85; P = 0.016, respectively) than children aged 24 to 59 months. CONCLUSION: The prevalence of malaria infection among children in the study area was comparable to the national level. In addition to available malaria control programmes, further attention should be paid to children whose mothers have no formal education, children aged 24 to 59 months, and children of mothers that are exposed to IPV in the area.
Subject(s)
Farmers/statistics & numerical data , Malaria/epidemiology , Child, Preschool , Cross-Sectional Studies , Diagnostic Tests, Routine , Female , Humans , Infant , Malawi/epidemiology , Male , Mothers , Prevalence , Risk Factors , Surveys and QuestionnairesABSTRACT
OBJECTIVE: The Global FKRP Registry is a database for individuals with conditions caused by mutations in the Fukutin-Related Protein (FKRP) gene: limb girdle muscular dystrophy R9 (LGMDR9, formerly LGMD2I) and congenital muscular dystrophies MDC1C, Muscle-Eye-Brain Disease and Walker-Warburg Syndrome. The registry seeks to further understand the natural history and prevalence of FKRP-related conditions; aid the rapid identification of eligible patients for clinical studies; and provide a source of information to clinical and academic communities. METHODS: Registration is patient-initiated through a secure online portal. Data, reported by both patients and their clinicians, include: age of onset, presenting symptoms, family history, motor function and muscle strength, respiratory and cardiac function, medication, quality of life and pain. RESULTS: Of 663 registered participants, 305 were genetically confirmed LGMDR9 patients from 23 countries. A majority of LGMDR9 patients carried the common mutation c.826C > A on one or both alleles; 67.9% were homozygous and 28.5% were compound heterozygous for this mutation. The mean ages of symptom onset and disease diagnosis were higher in individuals homozygous for c.826C > A compared with individuals heterozygous for c.826C > A. This divergence was replicated in ages of loss of running ability, wheelchair-dependence and ventilation assistance; consistent with the milder phenotype associated with individuals homozygous for c.826C > A. In LGMDR9 patients, 75.1% were currently ambulant and 24.6%, nonambulant (unreported in 0.3%). Cardiac impairment was reported in 23.2% (30/129). INTERPRETATION: The Global FKRP Registry enables the collection of patient natural history data, which informs academics, healthcare professionals and industry. It represents a trial-ready cohort of individuals and is centrally placed to facilitate recruitment to clinical studies.
Subject(s)
Muscular Dystrophies, Limb-Girdle/genetics , Pentosyltransferases/genetics , Registries , Walker-Warburg Syndrome/genetics , Adolescent , Adult , Age of Onset , Aged , Child , Cohort Studies , Female , Humans , Male , Middle Aged , Muscular Dystrophies, Limb-Girdle/physiopathology , Phenotype , Walker-Warburg Syndrome/physiopathology , Young AdultABSTRACT
INTRODUCTION: This article reports on the micro-, meso-, and macro-level impacts of sharing digital stories created by Indigenous youth leaders about HIV prevention activism in Canada. METHOD: Eighteen participants created digital stories and hosted screenings in their own communities to foster dialogue. Data for this article are drawn from individual semistructured interviews with the youth leaders, audio-recordings of audience reflections, and research team member's field notes collected between 2012 and 2015 across Canada. Data were coded using NVivo. A content analysis approach guided analysis. RESULTS: The process of sharing their digital stories had a positive impact on the youth themselves and their communities. Stories also reached policymakers. They challenged conventional public health messaging by situating HIV in the context of Indigenous holistic conceptions of health. DISCUSSION: The impact(s) of sharing digital stories were felt most strongly by their creators but rippled out to create waves of change for many touched by them. More research is warranted to examine the ways that the products of participatory visual methodologies can be powerful tools in creating social change and reducing health disparities.
Subject(s)
HIV Infections , Public Health , Adolescent , Canada , HIV Infections/prevention & control , HumansABSTRACT
This article studies the ways in which researchers working in the area of health and social research and using participatory visual methods might extend the reach of participant-generated creations such as photos and drawings to engage community leaders and policy-makers. Framed as going 'beyond engagement', the article explores the idea of the production of researcher-led digital dialogue tools, focusing on one example, based on a series of visual arts-based workshops with children from eight slums in Nairobi addressing issues of safety, security, and well-being in relation to housing. The authors conclude that there is a need for researchers to embark upon the use of visual tools to expand the life and use of visual productions, and in particular to ensure meaningful participation of communities in social change.
Subject(s)
Audiovisual Aids , Community-Based Participatory Research/methods , Poverty Areas , Psychology, Child , Safety , Art , Child , Community-Based Participatory Research/organization & administration , Computer Graphics , Humans , Kenya , Photography , Video RecordingABSTRACT
South Africa has been experiencing an epidemic of gender-based violence (GBV) for a long time and in some rural communities health workers, who are trained to care for those infected with HIV, are positioned at the forefront of addressing this problem, often without the necessary support. In this article, we pose the question: How might cultural production through media making with community health workers (CHWs) contribute to taking action to address GBV and contribute to social change in a rural community? This qualitative participatory arts-based study with five female CHWs working from a clinic in a rural district of South Africa is positioned as critical research, using photographs in the production of media posters. We offer a close reading of the data and its production and discuss three data moments: CHWs drawing on insider cultural knowledge; CHWs constructing messages; and CHWs taking action. In our discussion, we take up the issue of cultural production and then offer concluding thoughts on 'beyond engagement' when the researchers leave the community.
Subject(s)
Community Health Workers/organization & administration , Community-Based Participatory Research/methods , Gender-Based Violence/prevention & control , HIV Infections/prevention & control , Health Promotion/methods , Political Activism , Quality of Health Care/standards , Sexual Behavior , Community Health Workers/psychology , Community-Based Participatory Research/organization & administration , Female , Gender-Based Violence/economics , Gender-Based Violence/trends , HIV Infections/epidemiology , HIV Infections/transmission , Health Promotion/organization & administration , Humans , Organizational Case Studies , Qualitative Research , Quality of Health Care/trends , Rural Population , Socioeconomic Factors , South Africa/epidemiologyABSTRACT
This Introduction serves to map out a range of participatory visual approaches, as well as critical issues related to the use of participatory visual methodologies in global health. In so doing, it offers both an overview of these innovative practices in global health and a consideration of some of the key questions that researchers might ask themselves in design and implementation.
Subject(s)
Audiovisual Aids , Community-Based Participatory Research , Global Health , Health Policy/trends , Health Promotion/methods , Health Services Research/methods , Telecommunications , Art , Drama , Humans , Maps as Topic , Social Change , Video RecordingABSTRACT
This article outlines processes followed during a two-day offsite retreat for nurse faculty planned for the purpose of curricular redesign and content mapping. Faculty identified and leveled content for all baccalaureate clinical courses and engaged in dialogue specific to promoting student connections between didactic and clinical outcomes. Faculty developed two core simulation scenarios for every clinical course and leveled learning outcomes for each. Faculty defined where within the curriculum key concepts were introduced and planned depth of knowledge, application, and synthesis from sophomore through senior levels. Evaluation revealed the process led faculty to a stronger overall understanding of the curriculum.
Subject(s)
Curriculum , Education, Nursing, Baccalaureate/organization & administration , Faculty, Nursing/organization & administration , Health Care Reform/organization & administration , Concept Formation , Humans , Nursing Education Research , United StatesABSTRACT
Focusing on gender, race and colonialism, this paper foregrounds the voices of Indigenous young people, their histories of oppression, their legacies of resistance and the continuing strengths rooted in Indigenous peoples, their cultures and their communities. Exploring the relationship between gender and colonialism, the paper speaks to the lived realities of young people from Indigenous communities across Canada. Over 85 young people participated in six different Indigenous community workshops to create artistic pieces that explored the connections between HIV, individual risk and structural inequalities. In the course of the research, Indigenous young people, and young Indigenous women in particular, talked about how gender intersects with race and colonisation to create experiences that are, at times, especially difficult for them. In this paper, young people discuss the ways in which colonialism has demeaned women's roles and degraded women's sexuality, and how continuing cultural erasure and assimilationist policies impact on their lives and on their bodies.
Subject(s)
Attitude to Health/ethnology , Colonialism , HIV Infections/prevention & control , Health Promotion/methods , Indians, North American/statistics & numerical data , Adult , Canada , Cultural Characteristics , Female , Health Services, Indigenous/organization & administration , Humans , Male , Young AdultABSTRACT
BACKGROUND: As nursing and healthcare become more global, supported by technology, the opportunities for distance mentoring increase. Mentorship is critical to nurse educator recruitment and retention. STUDY OBJECTIVE: The purpose of this study was to identify communication practices of nurse educators involved in mentoring at a distance. DESIGN/SETTINGS: A qualitative design, utilizing in-person or telephone interviews was used. Participants were twenty-three protégés or mentors who were part of a yearlong distance mentoring program. ANALYSIS METHOD: An iterative process of hermeneutic analysis identified three themes; this paper focuses on the theme of connectedness. RESULTS: Participant narratives illuminate practices of connecting at a distance: meeting face-to-face, sharing personal information, experiencing reciprocity, journaling, being vulnerable, establishing one's presence, and appreciating different perspectives. CONCLUSION: Distance does not appear to limit the connecting potential leading to a meaningful mentoring relationship; rather, it offers possibilities that local mentoring relationships may not. Nurse educators in under-resourced countries, those in small programs without a cadre of senior faculty, and students in distance programs are among those who stand to benefit from distance mentoring relationships.
Subject(s)
Communication , Education, Distance , Education, Nursing/methods , Interprofessional Relations , Mentors , Faculty, Nursing , Humans , Interviews as Topic , Models, Educational , United StatesABSTRACT
Young adults often lack access to confidential, long-lasting, and nonjudgmental interactions with sexual health professionals at brick-and-mortar clinics. To ensure that patients return for their STI test results, post-result counseling, and STI-related information, computer-mediated health intervention programming allows them to receive sexual health information through onsite computers, the Internet, and mobile phone calls and text messages. To determine whether young adults (age: M = 21 years) prefer to communicate with health professionals about the status of their sexual health through computer-mediated communication devices, 303 second-year university students (183 from an urban North American university and 120 from a periurban university in South Africa) completed a paper-based survey indicating how they prefer to communicate with doctors and nurses: talking face to face, mobile phone call, text message, Internet chat programs, Facebook, Twitter, or e-mail. Nearly all students, and female students in South Africa in particular, prefer to receive their STI test results, post-results counseling, and STI-related information by talking face to face with doctors and nurses rather than communicating through computers or mobile phones. Results are clarified in relation to gender, availability of various technologies, and prevalence of HIV in Canada and in South Africa.
Subject(s)
Communication , Counseling/methods , Nurse-Patient Relations , Patient Preference/statistics & numerical data , Physician-Patient Relations , Sexually Transmitted Diseases/diagnosis , Sexually Transmitted Diseases/therapy , Adolescent , Adult , Canada , Cell Phone , Electronic Mail , Female , Health Care Surveys , Humans , Internet , Male , Middle Aged , Social Media , South Africa , Text Messaging , Young AdultABSTRACT
Staff development departments are challenged with addressing the entry of new graduates into the work force, updating the competencies of practicing nurses, and providing nurses with educational support to reduce turnover. Knowing how to develop simulations, integrate them into teaching, and effectively assess simulated performance is becoming a core role for educators in health care. For many educators, a knowledge and skill gap exists between the demand for simulation and competence in developing and using simulation. This article shares a cost-effective, three-step train-the-trainer model to prepare nurse educators to use simulation effectively. The three steps include champion identification, champion development, and champion integration. Strategies for addressing the challenges and lessons learned in implementing this model are outlined. The model is an effective and efficient approach for developing a core of champions in any topic area. These champions can then mentor and train others throughout the organization.
Subject(s)
Education, Nursing/methods , Faculty, Nursing , Staff Development/methods , Humans , Models, Educational , Program Development , Program Evaluation , United StatesABSTRACT
Mentoring is important for the recruitment and retention of qualified nurse faculty, their ongoing career development, and leadership development. However, what are current best practices of mentoring? The purpose of this paper is to provide an overview of a model for excellence in establishing a formal mentoring program for academic nurse educators. Six themes for establishing a formal mentoring program are presented, highlighting best practices in mentoring as culled from experience and the literature. Themes reflect aims to achieve appropriately matched dyads, establish clear mentorship purpose and goals, solidify the dyad relationship, advocate for and guide the protégé, integrate the protégé into the academic culture, and mobilize institutional resources for mentoring support. Attending to the six themes will help mentors achieve important protégé outcomes, such as orientation to the educator role, integration into the academic community, development of teaching, scholarship, and service skills, as well as leadership development. The model is intended to be generalizable for faculty teaching in a variety of academic nursing institution types and sizes. Mentoring that integrates the six themes assists faculty members to better navigate the academic environment and more easily transition to new roles and responsibilities.
ABSTRACT
Rapamycin is an antibiotic inhibiting eukaryotic cell growth and proliferation by acting on target of rapamycin (TOR) kinase. Mammalian TOR (mTOR) is thought to work through 2 independent complexes to regulate cell size and cell replication, and these 2 complexes show differential sensitivity to rapamycin. Here we combine functional genetics and pharmacological treatments to analyze rapamycin-sensitive mTOR substrates that are involved in cell proliferation and tissue regeneration after partial hepatectomy in mice. After hepatectomy, hepatocytes proliferated rapidly, correlating with increased S6 kinase phosphorylation, while treatment with rapamycin derivatives impaired regeneration and blocked S6 kinase activation. In addition, genetic deletion of S6 kinase 1 (S6K1) caused a delay in S phase entry in hepatocytes after hepatectomy. The proliferative defect of S6K1-deficient hepatocytes was cell autonomous, as it was also observed in primary cultures and hepatic overexpression of S6K1-rescued proliferation. We found that S6K1 controlled steady-state levels of cyclin D1 (Ccnd1) mRNA in liver, and cyclin D1 expression was required to promote hepatocyte cell cycle. Notably, in vivo overexpression of cyclin D1 was sufficient to restore the proliferative capacity of S6K-null livers. The identification of an S6K1-dependent mechanism participating in cell proliferation in vivo may be relevant for cancer cells displaying high mTOR complex 1 activity and cyclin D1 accumulation.
Subject(s)
Antibiotics, Antineoplastic/pharmacology , Cell Proliferation/drug effects , Liver Regeneration/physiology , Liver/drug effects , Liver/physiology , Ribosomal Protein S6 Kinases, 90-kDa/metabolism , Sirolimus/pharmacology , Animals , Cell Cycle/drug effects , Cell Cycle/physiology , Cells, Cultured , Cyclin D1/genetics , Cyclin D1/metabolism , Genotype , Hepatectomy , Hepatocytes/cytology , Hepatocytes/physiology , Isoenzymes/genetics , Isoenzymes/metabolism , Liver/cytology , Mechanistic Target of Rapamycin Complex 1 , Mice , Mice, Inbred C57BL , Mice, Knockout , Multiprotein Complexes , Proteins/metabolism , Ribosomal Protein S6 Kinases, 90-kDa/genetics , TOR Serine-Threonine KinasesABSTRACT
CD44 isoforms act as coreceptors for the receptor tyrosine kinases c-Met and VEGFR-2. However, Cd44 knockout mice do not show overt phenotypes, in contrast to Met and Vegfr-2 knockout mice. We hypothesized that CD44 is being compensated for by another factor in Cd44 null mice. Using RNAi technology and blocking experiments with antibodies, peptides, and purified ectodomains, as well as overexpression studies, we identified intercellular adhesion molecule-1 (ICAM-1) as a new coreceptor for c-Met in CD44-negative tumor cells and in primary hepatocytes obtained from Cd44 null mice. Most strikingly, after partial hepatectomy, CD44v6-specific antibodies inhibited liver cell proliferation and c-Met activation in wild-type mice, whereas ICAM-1-specific antibodies interfered with liver cell proliferation and c-Met activation in Cd44 knockout mice. These data show that ICAM-1 compensates for CD44v6 as a coreceptor for c-Met in Cd44 null mice. Compensation of proteins by members of the same family has been widely proposed to explain the lack of phenotype of several knockout mice. Our experiments demonstrate the functional substitution of a protein by a heterologous one in a knockout mouse.
Subject(s)
Hepatocytes/metabolism , Hyaluronan Receptors/metabolism , Intercellular Adhesion Molecule-1/metabolism , Protein Isoforms/metabolism , Proto-Oncogene Proteins c-met/metabolism , Receptor Cross-Talk , Signal Transduction , Vascular Endothelial Growth Factor Receptor-2/metabolism , Animals , Antibodies, Blocking/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Gene Silencing/drug effects , Genetic Complementation Test , Hepatocyte Growth Factor/metabolism , Hepatocyte Growth Factor/pharmacology , Hepatocytes/cytology , Hyaluronan Receptors/genetics , Intercellular Adhesion Molecule-1/genetics , Male , Mice , Mice, Knockout , Phenotype , Primary Cell Culture , Protein Isoforms/genetics , Protein Structure, Tertiary , Proto-Oncogene Proteins c-met/genetics , RNA, Small Interfering/pharmacology , Vascular Endothelial Growth Factor Receptor-2/geneticsABSTRACT
It has been suggested that increasing age is correlated with an acceleration of the progression of liver fibrosis induced by various agents, such as hepatitis C virus or chronic alcohol consumption. However, the cellular and molecular changes underlying this predisposition are not entirely understood. In the context of an aging population, it becomes challenging to decipher the mechanisms responsible for this higher susceptibility of older individuals to this acquired liver disorder. To address this issue, we induced liver fibrosis by carbon tetrachloride (CCl(4)) chronic administration to 8-week- and 15-month-old mice. We confirmed that susceptibility to fibrosis development increased with age and showed that aging did not affect fibrosis resolution capacity. We then focused on the impairment of hepatocyte proliferation, oxidative stress, and inflammation as potential mechanisms accelerating the development of fibrosis in the elderly. We detected no inhibition of hepatocyte proliferation after CCl(4) injury in 15-month-old mice, whereas it was inhibited after a partial hepatectomy. Finally, we observed that, in a context in which liver oxidative stress was not differentially increased in both experimental groups, there was a higher recruitment of inflammatory cells, including mostly macrophages and lymphocytes, oriented toward a T helper 2 (T(H)2) response in older mice. Our data show that in conditions of equivalent levels of oxidative stress and maintained hepatocyte proliferative capacity, an increased inflammatory reaction mainly composed of CD4(+) lymphocytes and macrophages expressing T(H)2 cytokines is the main factor involved in the higher susceptibility to fibrosis with increasing age.
Subject(s)
Aging/pathology , Disease Susceptibility , Inflammation/complications , Inflammation/pathology , Liver Cirrhosis/complications , Liver Cirrhosis/pathology , Animals , Carbon Tetrachloride , Cell Proliferation , Chronic Disease , Hepatocytes/pathology , Humans , Male , Mice , Mice, Inbred C57BL , Necrosis , Oxidative StressABSTRACT
GH is a pleiotropic hormone that plays a major role in proliferation, differentiation, and metabolism via its specific receptor. It has been previously suggested that GH signaling pathways are required for normal liver regeneration but the molecular mechanisms involved have yet to be determined. The aim of this study was to identify the mechanisms by which GH controls liver regeneration. We performed two thirds partial hepatectomies in GH receptor (GHR)-deficient mice and wild-type littermates and showed a blunted progression in the G(1)/S transition phase of the mutant hepatocytes. This impaired liver regeneration was not corrected by reestablishing IGF-1 expression. Although the initial response to partial hepatectomy at the priming phase appeared to be similar between mutant and wild-type mice, cell cycle progression was significantly blunted in mutant mice. The main defect in GHR-deficient mice was the deficiency of the epidermal growth factor receptor activation during the process of liver regeneration. Finally, among the pathways activated downstream of GHR during G(1) phase progression, namely Erk1/2, Akt, and signal transducer and activator of transcription 3, we only found a reduced Erk1/2 phosphorylation in mutant mice. In conclusion, our results demonstrate that GH signaling plays a major role in liver regeneration and strongly suggest that it acts through the activation of both epidermal growth factor receptor and Erk1/2 pathways.