Insulin-like growth factor I (IGF-I) and transforming growth factor-β1 (TGF-β1) are upregulated in myofibroblasts at sites of fibrosis in experimental enterocolitis and in Crohn's disease (CD). We compared the sites of expression of IGF-I and TGF-β1 in a rat peptidoglycan-polysaccharide (PG-PS) model of chronic granulomatous enterocolitis and fibrosis. We used the human colonic CCD-18Co fibroblast/myofibroblast cell line to test the hypothesis that TGF-β1 and IGF-I interact to regulate proliferation, collagen synthesis, and activated phenotype typified by expression of α-smooth muscle actin and organization into stress fibers. IGF-I potently stimulated while TGF-β1 inhibited basal DNA synthesis. TGF-β1 and IGF-I each had similar but not additive effects to induce type I collagen. TGF-β1 but not IGF-I potently stimulated expression of α-smooth muscle actin and stress fiber formation. IGF-I in combination with TGF-β1 attenuated stress fiber formation without reducing α-smooth muscle actin expression. Stress fibers were not a prerequisite for increased collagen synthesis. TGF-β1 upregulated IGF-I mRNA, which led us to examine the effects of IGF-I in cells previously activated by TGF-β1 pretreatment. IGF-I potently stimulated proliferation of TGF-β1-activated myofibroblasts without reversing activated fibrogenic phenotype. We conclude that TGF-β1 and IGF-I both stimulate type I collagen synthesis but have differential effects on activated phenotype and proliferation. We propose that during intestinal inflammation, regulation of activated phenotype and proliferation may require sequential actions of TGF-β1 and IGF-I, but they may act in concert to increase collagen deposition.
ABSTRACT Here, we use recent U.S. National Institutes of Health (NIH) data to document trends in the NIH‐funded workforce over time. Consistent with previous studies that were initiated by NIH, we find that the number of scientists funded on competing R01‐equivalent (R01 Eq.) and research project grants (RPGs) increased 2–5% per year between 2009 and 2016. Primary beneficiaries of this growth were experienced investigators (Exps), whereas the share of funding awarded to early‐stage investigators (ESIs) and new investigators (NIs) declined. The decline occurred even after NIH instituted the New and Early‐Stage Investigator policy in 2009. When we evaluate the investigator pool, we find that women and racial and ethnic minorities represent a higher percentage of NIs and ESIs relative to Exps. Thus, trends of diminishing support for NIs and ESIs may negatively impact the diversity of the current and future biomedical research workforce. We find some recent gains among women and Hispanics as part of the applicant and awardee pool for both R01 Eq. and RPGs, but significant, large gaps persist among nationally underrepresented racial minorities. Our findings suggest a need to prioritize investments and support of ESIs and NIs, groups in which women and racial and ethnic minorities represent a larger proportion of the applicant pool, to enhance diversity in the NIH‐funded workforce.—Nikaj, S., Roychowdhury, D., Lund, P. K., Matthews, M., Pearson, K. Examining trends in the diversity of the U.S. National Institutes of Health participating and funded workforce. FASEB J. 32, 6410–6422 (2018). www.fasebj.org
Postdoctoral training in the biological sciences continues to be an important credential for academic careers. Traditionally, this training is focused on an independent research experience. In this article, we describe a postdoctoral training program designed to prepare postdoctoral scholars for the responsibilities of an academic career that balances both research and teaching. The results showed that the research productivity of the postdoctoral scholars involved in the program was not statistically different from that of a comparison group of postdoctoral scholars not in the program. The measures of productivity including scientific seminars presented, students mentored, service contributions, and engagement in professional development activities were significantly greater for the scholars in the program. Moreover, the scholars in the program obtained faculty positions at a threefold greater rate than did a national sample of postdoctoral scholars. This study demonstrates the value of a structured program that combines research and teaching opportunities and serves as a model for aligning training initiatives with specific career trajectories.
While women have been well represented in medical school and biomedical doctoral degree programs, they do not comprise half of academic medicine faculty positions. Furthermore, there is a significant paucity of women in academic medicine leadership positions, as evidenced by the fact that only 16% of dean positions at United States Medical schools are filled by women. In this commentary, the authors review the state of women in academic medicine and argue that increased representation of women in the academic workforce will lead to economic gains, increased scientific discovery, and improvements to women's health.
The liver is a major source of circulating insulin-like growth factor I (IGF-I), and it also synthesizes several classes of IGF binding proteins (IGFBPs). Synthesis of IGF-I and IGFBPs is regulated by hormones, growth factors, and cytokines. They are nutritionally regulated and expressed in developmentally specific patterns. To gain insight into cellular regulatory mechanisms that determine hepatic synthesis of IGF-I and IGFBPs and to identify potential target cells for IGF-I within the liver, we studied the cellular sites of synthesis of IGF-I, IGF receptor, growth hormone (GH) receptor, and IGFBPs in freshly isolated rat hepatocytes, endothelial cells, and Kupffer cells. We also localized cellular sites of IGFBP synthesis by in situ hybridization histochemistry. Western ligand and immunoblot analyses were used to determine IGFBP secretion by isolated cells. Two IGF-I mRNA subtypes with different 5′ ends (class 1 and class 2) were detected in all isolated liver cell preparations. Type 1 IGF receptor mRNA was detected in endothelial cells, indicating that these cells are a local target for IGF actions in liver. GH receptor was expressed in all cell preparations, consistent with GH regulation of IGF-I and IGFBP synthesis in multiple liver cell types. The IGFBPs expressed striking cell-specific expression. IGFBP-1 was synthesized only in hepatocytes, and IGFBP-3 was expressed in Kupffer and endothelial cells. IGFBP-4 was expressed at high levels in hepatocytes and at low levels in Kupffer and endothelial cells. Cell-specific expression of distinct IGFBPs in the liver provides the potential for cell-specific regulation of hepatic and endocrine actions of IGF-I.
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