Expression of nerve growth factor messenger RNA in pancreatic cancer tissues in Sprague Dawley rats

Background Previous studies have demonstrated that nerve growth factor (NGF) is an important mediator of pathologic pain. Many studies have focused on cutaneous mechanisms for NGF-induced hyperalgesia; few have examined its contribution in deeper tissues like muscle. This study examined pain behaviors and the expression of NGF in incised hind paw flexor digitorum brevis muscle. Methods Adult Sprague-Dawley rats were pretreated with anti-NGF peptibody and underwent skin or skin plus deep fascia and muscle incision. Guarding pain behaviors were measured. Muscle NGF messenger RNA (mRNA) was measured by reverse-transcriptase polymerase chain reaction. Changes in NGF protein expression were measured using Western blot, enzyme-linked immunosorbent assay, and immunohistochemistry. In situ hybridization for NGF mRNA was also performed. Results Pretreatment with anti-NGF peptibody (100 mg/kg) decreased the guarding behavior caused by deep fascia and muscle incision. Muscle NGF mRNA increased abruptly 2 h after incision and was the same as control by postoperative day 1. NGF protein increased from 4 h after incision and was sustained for several days. NGF was localized in many calcitonin gene-related peptide-positive axons, few N52-positive axons, but not isolectin B4-positive axons in incised muscle. The sources of NGF mRNA included keratinocytes in epidermis and fibroblasts in deeper tissues. Conclusion Fibroblasts adjacent to the injury are sources of NGF in incised muscle. NGF is upregulated by incision of muscle and contributes to guarding pain behavior.

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Retrobulbar administration of purified anti-nerve growth factor in developing rats induces structural and biochemical changes in the retina and cornea

International Journal of Ophthalmology ◽

10.18240/ijo.2021.02.05 ◽

2021 ◽

Vol 14 (2) ◽

pp. 209-216

Author(s):

Luigi Aloe ◽

◽

Bijorn Omar Balzamino ◽

Graziana Esposito ◽

Alessandra Micera ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Protein Expression ◽

Protein Profile ◽

Quick Response ◽

Sprague Dawley ◽

Compensatory Mechanisms ◽

Nerve Growth ◽

Sprague Dawley Rats ◽

Molecular Expression

AIM: To develop an experimental model of endogenous nerve growth factor (NGF) deprivation by retrobulbar administration of purified neutralizing anti-NGF antibodies in young Sprague-Dawley rats and provide further information on NGF expression in the retina and cornea. METHODS: Sixty old pathogen-free Sprague Dawley rats (p14, post-natal days) were treated with repeated retrobulbar injections of neutralizing anti-NGF (2 µL, 100 µg/mL, every 3d). After 2wk (p28), retinal and corneal tissues were investigated for morphological, biochemical, and molecular expression of trkANGFR by using Western blotting or immunofluorescence. Rhodopsin as well as protein profile expression were also investigated. RESULTS: Chronic retrobulbar neutralizing anti-NGF antibodies changed the distribution of trkANGFR immunoreactivity at retinal level, while no changes were detected for global trkANGFR protein expression. By contrary, the treatment resulted in the increase of corneal trkANGFR expression. Retinal tissues showed a decreased rhodopsin expression as well as reduced number of both rhodopsin expressing and total retinal cells, as observed after single cell extraction. A decreased expression of ICAM-1, IL-17 and IL-13 as well as an increased expression of IL-21 typified retinal extracts. No significant changes were observed for corneal tissues. CONCLUSION: The reduced availability of endogenous NGF, as produced by chronic retrobulbar anti-NGF administration, produce a quick response from retinal tissues, with respect to corneal ones, suggesting the presence of early compensatory mechanisms to protect retinal networking.

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Effects of Monoclonal Antibodies against Nerve Growth Factor on Healthy Bone and Joint Tissues in Mice, Rats, and Monkeys: Histopathologic, Biomarker, and Microcomputed Tomographic Assessments

Toxicologic Pathology ◽

10.1177/0192623318772501 ◽

2018 ◽

Vol 46 (4) ◽

pp. 408-420 ◽

Cited By ~ 3

Author(s):

Kathryn E. Gropp ◽

Cathy S. Carlson ◽

Mark G. Evans ◽

Cedo M. Bagi ◽

William J. Reagan ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Sprague Dawley ◽

Nerve Growth ◽

Joint Replacements ◽

Total Joint Replacements ◽

Sprague Dawley Rats ◽

Clinical Hold ◽

High Doses ◽

Rat Study

Tanezumab, an anti-nerve growth factor (NGF) antibody, is in development for management of chronic pain. During clinical trials of anti-NGF antibodies, some patients reported unexpected adverse events requiring total joint replacements, resulting in a partial clinical hold on all NGF inhibitors. Three nonclinical toxicology studies were conducted to evaluate the effects of tanezumab or the murine precursor muMab911 on selected bone and joint endpoints and biomarkers in cynomolgus monkeys, Sprague-Dawley rats, and C57BL/6 mice. Joint and bone endpoints included histology, immunohistochemistry, microcomputed tomography (mCT) imaging, and serum biomarkers of bone physiology. Responses of bone endpoints to tanezumab were evaluated in monkeys at 4 to 30 mg/kg/week for 26 weeks and in rats at 0.2 to 10 mg/kg twice weekly for 28 days. The effects of muMab911 at 10 mg/kg/week for 12 weeks on selected bone endpoints were determined in mice. Tanezumab and muMab911 had no adverse effects on any bone or joint parameter. There were no test article–related effects on bone or joint histology, immunohistochemistry, or structure. Reversible, higher osteocalcin concentrations occurred only in the rat study. No deleterious effects were observed in joints or bones in monkeys, rats, or mice administered high doses of tanezumab or muMab911.

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Role of Nerve Growth Factor in Cutaneous Wound Healing: Accelerating Effects in Normal and Healing-impaired Diabetic Mice

Journal of Experimental Medicine ◽

10.1084/jem.187.3.297 ◽

1998 ◽

Vol 187 (3) ◽

pp. 297-306 ◽

Cited By ~ 148

Author(s):

Hiroshi Matsuda ◽

Hiromi Koyama ◽

Hiroaki Sato ◽

Junko Sawada ◽

Atsuko Itakura ◽

...

Keyword(s):

Wound Healing ◽

Nerve Growth Factor ◽

Growth Factor ◽

Granulation Tissue ◽

Messenger Rna ◽

Biological Activities ◽

Serum Levels ◽

Blood Stream ◽

Diabetic Mice ◽

Nerve Growth

Four full-thickness skin wounds made in normal mice led to the significant increase in levels of nerve growth factor (NGF) in sera and in wounded skin tissues. Since sialoadenectomy before the wounds inhibited the rise in serum levels of NGF, the NGF may be released from the salivary gland into the blood stream after the wounds. In contrast, the fact that messenger RNA and protein of NGF were detected in newly formed epithelial cells at the edge of the wound and fibroblasts consistent with the granulation tissue produced in the wound space, suggests that NGF was also produced at the wounded skin site. Topical application of NGF into the wounds accelerated the rate of wound healing in normal mice and in healing-impaired diabetic KK/Ta mice. This clinical effect of NGF was evaluated by histological examination; the increases in the degree of reepithelialization, the thickness of the granulation tissue, and the density of extracellular matrix were observed. NGF also increased the breaking strength of healing linear wounds in normal and diabetic mice. These findings suggested that NGF immediately and constitutively released in response to cutaneous injury may contribute to wound healing through broader biological activities, and NGF improved the diabetic impaired response of wound healing.

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