Cell proliferation in denervated muscle: Time course, distribution and relation to disuse

Neuroscience ◽  
1982 ◽  
Vol 7 (7) ◽  
pp. 1817-1822 ◽  
Author(s):  
M.A. Murray ◽  
N. Robbins
Keyword(s):  
Cell Proliferation ◽  
Time Course ◽  
Denervated Muscle

Abstract 160: Pim-1 Preserves Cardiac Stem Cell Proliferation with Age

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Michael McGregor ◽  
Shabana Din ◽  
Natalie Gude ◽  
Mark A Sussman
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Time Course ◽  
Protein A ◽  
Cell Types ◽  
Tissue Homeostasis ◽  
Dominant Negative ◽  
Repair Capacity ◽  
Tissue Samples ◽  
The Impact

Rationale Cardiac stem cells (CSC) regulate cardiomyogenesis and support regenerative processes in the heart, but aging adversely affects stem cell repair capacity. Aging is a primary cause of impaired cardiac function characterized by accumulation of senescent cells. CSC senescence is associated with permanent growth arrest that decreases survival signaling and cellular replacement, inevitably diminishing the capacity of the heart to maintain tissue homeostasis. Therefore, promoting CSC growth may improve cardiac performance with age. Pim-1 kinase exhibits protective and proliferative effects in the myocardium but the role of Pim-1 in cardiac aging has not been thoroughly studied. Objective Demonstrate that Pim-1 promotes stem cell growth in the aged myocardium correlating with increased expression of centromere protein A (CENP-A), a kinetochore-associated protein known to support cell proliferation in numerous species and cell types. Methods & Results CENP-A expression levels were evaluated from murine myocardial tissue samples ranging in age from 11 days post coitum to 4 months of age with analysis by immunoblot as well as quantitative PCR. CENP-A expression was colocalized with c-kit as a marker of CSC by immunohistochemical labeling, revealing a decline in CENP-A expression over the time course of postnatal myocardial maturation. The impact of Pim-1 upon CENP-A level was assessed by comparative analysis of non-transgenic mice versus genetically modified transgenic mouse lines expressing either Pim-1 (wild type) or a dominant negative functionally dead Pim-1 mutant. Pim-1 overexpression increases persistence of CENP-A in CSCs with age, as well as the prevalence of cycling CSCs as marked by phosph-H3 expression, while the functionally dead mutant accelerates CENP-A diminution and decreases CSC proliferation. Conclusion CENP-A decline in c-kit positive cells with age provides intriguing evidence of a potential mechanism for the diminished capacity of CSCs to maintain tissue homeostasis. Pim-1 mitigates CENP-A diminution, demonstrating the promising potential of Pim-1 to promote cardiac growth and repair with age.

Keratinocyte growth factor therapy in murine oleic acid-induced acute lung injury

2005 ◽  
Vol 288 (6) ◽  
pp. L1179-L1192 ◽  
Author(s):  
K. Ulrich ◽  
M. Stern ◽  
M. E. Goddard ◽  
J. Williams ◽  
J. Zhu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acute Lung Injury ◽  
Gene Delivery ◽  
Lung Injury ◽  
Time Course ◽  
Lung Compliance ◽  
Alveolar Type ◽  
Protein Therapy ◽  
Cell Numbers ◽  
Atii Cell

Alveolar type II (ATII) cell proliferation and differentiation are important mechanisms in repair following injury to the alveolar epithelium. KGF is a potent ATII cell mitogen, which has been demonstrated to be protective in a number of animal models of lung injury. We have assessed the effect of recombinant human KGF (rhKGF) and liposome-mediated KGF gene delivery in vivo and evaluated the potential of KGF as a therapy for acute lung injury in mice. rhKGF was administered intratracheally in male BALB/c mice to assess dose response and time course of proliferation. SP-B immunohistochemistry demonstrated significant increases in ATII cell numbers at all rhKGF doses compared with control animals and peaked 2 days following administration of 10 mg/kg rhKGF. Protein therapy in general is very expensive, and gene therapy has been suggested as a cheaper alternative for many protein replacement therapies. We evaluated the effect of topical and systemic liposome-mediated KGF-gene delivery on ATII cell proliferation. SP-B immunohistochemistry showed only modest increases in ATII cell numbers following gene delivery, and these approaches were therefore not believed to be capable of reaching therapeutic levels. The effect of rhKGF was evaluated in a murine model of OA-induced lung injury. This model was found to be associated with significant alveolar damage leading to severe impairment of gas exchange and lung compliance. Pretreatment with rhKGF 2 days before intravenous OA challenge resulted in significant improvements in Po2, Pco2, and lung compliance. This study suggests the feasibility of KGF as a therapy for acute lung injury.

PCNA and total nuclear protein content as markers of cell proliferation in pea tissue

1992 ◽  
Vol 102 (1) ◽  
pp. 71-78 ◽  
Author(s):  
SANDRA CITTERIO ◽  
SERGIO SGORBATI ◽  
MARISA LEVI ◽  
BRUNO MARIA COLOMBO ◽  
ELIO SPARVOLI
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Protein Content ◽  
Time Course ◽  
Nuclear Protein ◽  
Flow Cytometric Analysis ◽  
Nuclear Antigen ◽  
Cycle Phase ◽  
Proliferating Cells ◽  
Embryo Cells

The identification of cell proliferation markers has been shown to be a useful tool with which to study basic mechanisms of cell cycle progression. The use of immunofluorescence techniques revealed the presence of the proliferating cell nuclear antigen (PCNA) in pea tissue, where we observed a high PCNA expression in proliferating cells of the root meristem compared to noncycling cells of the differentiated leaf. The presence of PCNA was monitored also during the time-course of seed germination, before, during and after the cell cycle resumption of the embryo cells. PCNA is present in embryo cells not only during and after resumption of the cell cycle but also before, when cells have not yet begun replicating their genome. A bivariate flow cytometric analysis of DNA and nuclear protein content was used to localize precisely the cells of the examined pea tissues in different cell cycle phase subcompartments. A high correlation was found between the degree of cell proliferation and the protein content of G1 nuclei, on the one hand, and the percentage of PCNA positive cells on the other.

Deterministic Trigger of Self-Renewal in Expanded HSCs Expressing Hoxb4 + Antisense Pbx1.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 800-800
Author(s):  
Sonia Cellot ◽  
Jana Krosl ◽  
Keith Humphries ◽  
Guy Sauvageau
Keyword(s):  
Cell Proliferation ◽  
Stem Cell ◽  
Cell Fate ◽  
Time Course ◽  
Cell Cycle Distribution ◽  
Self Renewal ◽  
Primary Mouse ◽  
The Impact

Abstract We previously reported the generation of pluripotent and ultracompetitive HSCs through modulation of Hoxb4 and Pbx1 levels. These Hoxb4hiPbx1lo HSCs display a tremendous regenerative potential, yet they are still fully responsive to in vivo regulatory signals that control stem cell pool size (20 000 HSCmouse) and differentiation pathways. Further work in our laboratory attempted to circumvent these physiological constraints by expanding Hoxb4hiPbx1lo transduced HSCs in vitro, and hence revealing their intrinsic expansion potential. Independent experiments were performed where primary mouse BM cells were co-infected with retroviruses encoding antisense Pbx1 cDNA plus YFP, and Hoxb4 plus GFP (double gene transfer ranged between 20–50%). Hoxb4hiPbx1lo HSCs measured using the CRU assay expanded by 105-fold during a 12 day in vitro culture. Following serial transplantations, these cells displayed an additional 4–5 log expansion in vivo. Total stem cell content per animal remained within normal limits. Southern blot analyses of proviral integrations showed that the expansion was polyclonal, and analyses of individually expanded clones provided a molecular proof of in vitro self-renewal (SR). This unprecedented level of HSC expansion in such a short time course (105-fold in 12 days) implies an absolute HSC doubling time of approximately 17 hours in our culture, raising the possibility that virtually all dividing HSCs undergo self-renewal. This analysis prompted us to dissect the impact of Hoxb4 on cell proliferation versus cell fate (SR?). When analyzed during the period of maximal HSC expansion, the cell cycle distribution of Sca+ or Sca+Lin− cells were comparable between the cultures initiated with neo control versus Hoxb4 BM cells (CTL vs Hoxb4: G0/G1: 66% vs 83%; S: 15% vs 9%; G2/M: 18% vs 7%). Correspondingly, CFSE tracking studies confirmed the identical, or even lower, number of cellular divisions in Sca+ cells isolated from cultures initiated with Hoxb4 versus neo transduced cells. Annexin V studies precluded protection from apoptosis as the major mechanism to increase HSC numbers since similar results (3–10% positive cells) were observed in the Hoxb4 versus neo-transduced cells. In summary, our studies support the emerging concept that distinct molecular pathways regulate cell proliferation and self-renewal, suggesting that Hoxb4 + antisense Pbx1 predominantly triggers self-renewal over HSC proliferation.

scholarly journals Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation

2004 ◽  
Vol 32 (2) ◽  
pp. 397-414 ◽  
Author(s):  
JA Vendrell ◽  
F Magnino ◽  
E Danis ◽  
MJ Duchesne ◽  
S Pinloche ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cell Proliferation ◽  
Time Course ◽  
Cell Transformation ◽  
Expression Profiles ◽  
Estrogen Metabolism ◽  
Breast Carcinoma Cell Line ◽  
Human Breast ◽  
Estrogen Regulation

We explored, by cDNA mini-arrays, gene expression measurements of MVLN, a human breast carcinoma cell line derived from MCF-7, after 4 days of exposure to 17beta-estradiol (E(2)) treatment, in order to extend our understanding of the mechanism of the pharmacological action of estrogens. We focused on 22 genes involved in estrogen metabolism, cell proliferation regulation and cell transformation. The specificity of the E(2) response was reinforced by comparison with 4-hydroxytamoxifen (OH-Tam), ICI 182,780 and E(2)+OH-Tam expression profiles. Real-time quantitative PCR (RTQ-PCR) confirmed the variation of expression of known (TFF1, AREG, IRS1, IGFBP4, PCNA, ERBB2, CTSD, MYC) as well as novel (DLEU2, CCNA2, UGT1A1, ABCC3, ABCC5, TACC1, EFNA1, NOV, CSTA, MMP15, ZNF217) genes. The temporal response of these gene expression regulations was then investigated after 6 and 18 h of E(2) treatment and this allowed the identification of different time-course patterns. Cycloheximide treatment studies indicated first that estrogen affected the transcript levels of ABCC3 and ABCC5 through dissimilar pathways, and secondly that protein synthesis was needed for modulation of the expression of the CCNA2 and TACC1 genes by estrogens. Western blot analysis performed on TFF1, IRS1, IGFBP4, amphiregulin, PCNA, cyclin A2, TACC1 and ABCC5 proteins confirmed the mini-array and RTQ-PCR data, even for genes harboring low variations of mRNA expression. Our findings should enhance the understanding of changes induced by E(2) on the transcriptional program of human E(2)-responsive cells and permit the identification of new potential diagnostic/prognostic tools for the monitoring of estrogen-related disease conditions such as breast cancer.

Nutrient-stimulated GLP-2 release and crypt cell proliferation in experimental short bowel syndrome

2005 ◽  
Vol 288 (3) ◽  
pp. G431-G438 ◽  
Author(s):  
G. R. Martin ◽  
L. E. Wallace ◽  
B. Hartmann ◽  
J. J. Holst ◽  
L. Demchyshyn ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Time Course ◽  
Intestinal Adaptation ◽  
Intestinal Resection ◽  
Small Bowel Resection ◽  
Crypt Cell ◽  
Crypt Cell Proliferation ◽  
Proximal Intestine ◽  
The Relationship ◽  
Over Time

Glucagon-like peptide-2 (GLP-2) is an enteroendocrine peptide that is released in response to luminal nutrients and has unique trophic actions in the gastrointestinal tract. These features suggest GLP-2 may be important in controlling intestinal adaptation. We examined the relationship over time of GLP-2 production and adaptation to intestinal resection, the effects of resection-induced malabsorption on GLP-2 production, and the correlation of endogenous serum GLP-2 levels with adaptation as measured by crypt-cell proliferation (CCP). We initially examined the effect of nutrient malabsorption, induced by a 90% resection of the proximal intestine studied on day 4, on the time course and levels of GLP-2 release. Secondly, the degree of malabsorption was varied by performing intestinal transection or 50, 75, or 90% resection of proximal small intestine. Finally, the relationship of GLP-2 levels over time with adaptation to a 90% resection was examined by determining GLP-2 levels on days 7, 14, and 28, and correlating this with intestinal adaptation, as assessed by morphology and CCP rate. A 90% resection significantly increased basal and postprandial GLP-2 levels, with a net increase in nutrient-stimulated exposure over 90 min; GLP-2 exposure (integrated levels vs. time) increased 12.7-fold in resected animals ( P < 0.001). Basal and postprandial GLP-2 levels significantly correlated with the magnitude of intestinal resection ( r2 = 0.71; P < 0.001), CCP ( r2 = 0.48; P < 0.005), and nutrient malabsorption (protein, P < 0.001; fat, P < 0.005). The increase in CCP was maintained to 28 days after small bowel resection and was associated with an ongoing elevation in GLP-2 release. These findings suggest that GLP-2 is important in initiating and maintaining the small intestinal adaptive response to resection.

Time course of rat kidney cell proliferation and influence of endogenous inhibitors

1993 ◽  
Vol 115 (5) ◽  
pp. 575-577
Author(s):  
E. A. Shentseva ◽  
M. Ya. Shevtsova ◽  
A. B. Malyshev ◽  
V. N. Nikitin
Keyword(s):  
Cell Proliferation ◽  
Kidney Cell ◽  
Time Course ◽  
Rat Kidney ◽  
Endogenous Inhibitors

scholarly journals Improved Muscle Function After Injury with the Application of a Biological Decellularized Matrix

2020 ◽  
Author(s):  
Amina El Ayadi ◽  
Melody R.S. Threlkeld ◽  
Steven E. Wolf ◽  
Juquan Song
Keyword(s):  
Cell Proliferation ◽  
Muscle Cell ◽  
Muscle Function ◽  
Potential Benefit ◽  
Time Course ◽  
Isometric Force ◽  
Cell Proliferation And Differentiation ◽  
Function Recovery ◽  
Proliferation And Differentiation

Abstract Background: Skeletal muscle injury leads to loss of muscle function that lasts well into recovery and can be permanent. Application of the novel bio-scaffold termed porcine-derived urinary bladder matrix (UBM) has a potential benefit to mitigate injury through tissue regeneration. To date, findings of potential benefit in animal models were limited to short assessment times. The purpose of this study was to investigate whether UBM treatment 14 days after injury sustainably improves the recovery of muscle function in injured mice. Methods: C57BL/6 adult male mice received bilateral laceration injuries on the gastrocnemius (GN) muscle under anesthesia and were then treated with vehicle or 150 µg of UBM nanoparticles. Treatment was applied immediately after injury or 14 days later. Muscle isometric force was measured 60 days after injury. Previous time course analyses have shown that muscle function did not start to improve until after 42 days after injury. Therefore, we designed a second experiment to trace the time course of UBM effects on muscle function recovery by measuring the isometric muscle force at 49 and 90 days after injury. In vitro, we analyzed the effects of UBM on muscle cell proliferation and differentiation. Results: UBM promotes muscle cell proliferation and differentiation. Twitch (Pt), tetanic (Po) force and maximal fatigue were significantly decreased in the injured mice on day 60. Muscle fatigue maximum force significantly recovered when UBM treatment was applied 14 days after injury (p<0.05) but not when UBM was applied immediately after the injury. Time course analysis demonstrated that UBM improvement of Pt and Po was evident by day 49 after injury (p<0.05). However, no further muscle function improvement was observed on day 90. Conclusions: Delayed treatment with the UBM improves muscle function recovery following laceration injury starting 49 days after injury. These effects may be mediated by improvements in muscle cell proliferation and differentiation. This animal model is suitable to test other therapeutic strategies to improve muscle function after injury.

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