Collagen Proline Hydroxylase in Wound Healing, Granuloma Formation, Scurvy, and Growth

Mussini, E.; Hutton, John J.; Udenfriend, Sidney

doi:10.1126/science.157.3791.927

Cited by 184 publications

(57 citation statements)

References 15 publications

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“…In all the above cases a local insult or injury to the tissue specifically turns on collagen synthesis in that tissue. In the case of the skin, the initiation of collagen synthesis by an incision was actually localized to within a few millimeters of the wound (23). Hypertension may be considered another type of insult or injury, analogous to the above examples, which impinges on the entire vascular bed exposed to the increased pressure (2).…”

Section: Discussionmentioning

confidence: 99%

“…However, the specific increase in turnover of arterial collagen (about 4-fold) as a result of hypertension indicates that whatever central regulation there may be can be overridden by a local need. This is well known from studies of skin wounds (23), liver fibrosis (24), and lung fibrosis (25). In all the above cases a local insult or injury to the tissue specifically turns on collagen synthesis in that tissue.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Increased turnover of arterial collagen in hypertensive rats.

Nissen¹,

Cardinale²,

Udenfriend³

1978

Proc. Natl. Acad. Sci. U.S.A.

176

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The turnover of total collagen in several tissues of 12-week-old normotensive and hypertensive rats was estimated by using tritium-labeled proline as a precursor. The effect of reutilization of the label was minimized by treatment with large doses of unlabeled proline subsequent to administering the radioactive imino acid. The collagen from skin, tail tendon, aorta, and mesenteric artery in normotensive animals had a half-life of about 60-70 days. In hypertensive animals the half-lives of skin and tail tendon collagen were unchanged but the half-lives of collagen in the aorta and mesenteric artery were reduced to 17 days.In previous studies from this laboratory we reported that hypertension in rats leads to an increased synthesis and deposition of collagen in arteries (1) and microvessels (2). In one set of experiments, treatment of hypertensive rats with f-aminopropionitrile, an inhibitor of collagen crosslinking, resulted in a lowering of the blood pressure within 3 weeks (3). If collagen deposition itself leads to a maintenance of the elevated pressure as we have proposed (3), then this reversal in such a short time may indicate that in hypertension collagen breakdown as well as synthesis may be accelerated. To investigate this possibility, we set about to measure the decay in specific activity of protein-bound hydroxyproline (collagen) after rats were labeled with L-[2,3-3H]proline. Many other investigators have attempted to measure collagen turnover using radioactive amino acids (4-9); however, no correction was made for reutilization of the labeled amino acid that was used. In this report we have utilized an in vivo pulse-chase experiment to minimize the problem of reutilization and have been able to estimate the turnover of collagen in several tissues of normal and hypertensive rats. Normotensive rats (12-weeks-old) with an average body weight of 373 g were kept in disposable cages in a hood. DOCA/salt hypertension was produced in uninephrectomized 6-week-ole male Wistar rats by twice weekly subcutaneous injection of DOCA (5 mg per rat) (10, 11). Rats were maintained on the standard diet and allowed free access to drinking water containing 1% NaCl. After 6 weeks of treatment their average blood pressure was 200 mm Hg (1 mm Hg = 133 Pa) and their average body weight was 416 g. During the experiments, the normotensive animals gained 120 g in 53 days and 250 g in 111 days, while the hypertensives gained 90 g in 53 days. Of the twenty rats started on the DOCA/salt regimen, five died from respiratory infections and three others could not be used because they were also infected. For this reason only three time points could be measured for the hypertensive group. Blood pressure was monitored weekly by the tail cuff microphone method with an instrument made by Hoffmann-La Roche & Co., Basel, Switzerland. MATERIALS AND METHODSBlood was obtained by either cardiac puncture or tail vein bleeding. Serum proteins were precipitated by the addition of 3 ml of 10% trichloroacetic acid per ml of serum and removed ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Increased turnover of arterial collagen in hypertensive rats.

Nissen¹,

Cardinale²,

Udenfriend³

1978

Proc. Natl. Acad. Sci. U.S.A.

176

View full text Add to dashboard Cite

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“…These and other compounds in NM (i.e. vitamin C, lysine, proline, copper, manganese and N-acetyl cysteine) are important in supporting the integrity and stability of connective tissue through various mechanisms, thereby contributing to tumor encapsulation and curtailing cancer cells spread (14)(15)(16)(17)(18)(19)(20)(21)(22). In addition, NM components N-acetyl cysteine and selenium have been shown to inhibit tumor cell MMP-9 and invasive activities and migration of endothelial cells through the ECM (23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

Modulation of MMP-2 and −9 secretion by cytokines, inducers and inhibitors in human melanoma A-2058 cells

et al. 2017

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Abstract. Melanoma, an extremely aggressive cancer, causes the most skin cancer-related deaths, due to metastasis to other areas of the body, such as lymph nodes, lungs, liver, brain or bone. It is characterized by high levels of matrix metalloproteinase (MMP)-2 and -9 secretions that degrade the extracellular matrix and basement membrane, allowing cancer cells to spread to distal organs. Various cytokines, mitogens, growth factors, inducers and inhibitors control MMP activities. We investigated the roles of these in regulation of MMP-2 and -9 in human melanoma A-2058 cells. Human A-2058 cells were grown in DMEM supplemented with 15% FBS and antibiotics in 24-well tissue culture plates. At near confluence, the cells were washed with PBS and incubated in serum-free media with phorbol 12-myristate 13-acetate (PMA) at 10, 25, 50 and 100 ng/ml; TNF-α and IL-1β at 0.1, 1, 10 and 25 ng/ml; LPS at 10, 25, 50 and 100 µg/ml; epigallocatechin gallate (EGCG) and doxycycline (Dox) at 10, 25, 50 and 100 µM without and with PMA; a nutrient mixture (NM) containing lysine, proline, ascorbic acid and green tea extract without and with PMA at 10, 50, 100, 500 and 1,000 µg/ml; actinomycin D and cyclohexamide at 2 and 4 µM; retinoic acid and dexamethasone at 50 µM. After 24 h the media were removed and analyzed for MMP-2 and MMP-9 by zymography and densitometry. Melanoma A-2058 demonstrated strong expression of MMP-2 and slight expression of MMP-9. PMA at 100 ng/ml showed no effect on MMP-2 secretion but potently upregulated MMP-9 secretion to 400% that of control. TNF-α showed no significant overall effect on expression of MMP-2 but potent dose-dependent increased MMP-9 secretion with 200% of control at 25 ng/ml. IL-1β showed no significant effect on MMP-2 or MMP-9 secretion by A-2058 cells, except at 25 ng/ml where MMP-2 level was reduced by ~40% and MMP-9 secretion ~50%. LPS treatment showed no significant effect on MMP-2 secretion and enhanced MMP-9 secretion up to 25 µg/ml followed by decreased level. EGCG, NM and doxycycline, without and with PMA, downregulated the expression of MMP-2 and MMP-9 in a dose-dependent manner. Actinomycin D, cyclohexamide and retinoic acid had inhibitory effects on MMP-2, while dexamethasone showed slight stimulatory effect on MMP-2 secretion. Our results showed that select cytokines, mitogens and inhibitors modulated A-2058 MMP-2 and MMP-9 expression. They suggest the clinical potential of MMP inhibitors, especially the non-toxic ones, such as the nutrient mixture and its component EGCG in management of melanoma.

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“…Blood vessels supply oxygen and nutrients, which is essential to sustain the newly formed granulation tissue. As an example, the deposition of collagen relies on proline hydroxlyase, an oxygen-dependent enzyme 31 .…”

Section: Iib Proliferation and Tissue Formationmentioning

confidence: 99%

Anesthesia, Microcirculation, and Wound Repair in Aging

Bentov¹,

Reed²

2014

Survey of Anesthesiology

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Age related changes in skin contribute to impaired wound healing after surgical procedures. Changes in skin with age include decline in thickness and composition, a decrease in the number of most cell types and diminished microcirculation. The microcirculation provides tissue perfusion, fluid homeostasis, and delivery of oxygen and other nutrients. It also controls temperature and the inflammatory response. Surgical incisions cause further disruption of the microvasculature of aged skin. Perioperative management can be modified to minimize insults to aged tissues. Judicious use of fluids, maintenance of normal body temperature, pain control and increased tissue oxygen tension are examples of adjustable variables that support the microcirculation. Anesthetic agents influence the microcirculation from a combination of effects on cardiac output, arterial pressure and local micro-vascular changes. We examine the role of anesthetic management in optimizing the microcirculation and potentially improving postoperative wound repair in older persons. I. BackgroundSurgical wound repair is a major problem in the older population 1 , who are at increased risk of wound dehiscence and infection 2 . As a specific example, surgical site infections (SSI) are common (about 500,000 cases annually in the United States), lead to worse patient outcome (patients who develop SSI are twice as likely to die 3 ), and are an enormous economic burden (1-10 billion dollars annually) 4 . Many factors contribute to age related changes in skin 5 and subsequent vulnerability to impaired wound healing and infection. Changes in skin with age ( Figure 1) include a decline in epidermal and dermal thickness and composition, as well as a decrease in the number of most resident cell types. The dermalepidermal junction is flattened and the microcirculation is diminished 6 . The latter is defined as blood flow through arterioles, capillaries and venules and is the key system that affects the entire skin surface. In the aging patient, the skin's microcirculation is reduced by 40% between the ages of 20 to 70 years 7 . The microcirculation provides tissue perfusion, fluid hemostasis, and delivery of oxygen and other nutrients. It also controls temperature and the inflammatory response. Surgical incisions cause disruption of the skin's microcirculation as manifested by local edema resulting from vasodilation and increased vascular permeability. Summary StatementAged skin is at increased risk of poor post-operative wound healing. Changes in the cutaneous microcirculation with aging contribute to this risk. This review examines the role of anesthesia management on microcirculatory function. In this review, we will use skin as a representative organ to describe age-related changes that negatively affect the microcirculation and have subsequent impacts on wound healing and the incidence of postoperative infection. We will then examine the role of anesthesia management in minimizing detrimental effects on the microcirculation. A greater understanding of...

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Collagen Proline Hydroxylase in Wound Healing, Granuloma Formation, Scurvy, and Growth

Cited by 184 publications

References 15 publications

Increased turnover of arterial collagen in hypertensive rats.

Increased turnover of arterial collagen in hypertensive rats.

Modulation of MMP-2 and −9 secretion by cytokines, inducers and inhibitors in human melanoma A-2058 cells

Anesthesia, Microcirculation, and Wound Repair in Aging

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