Neurite Penetration into Collagen Gels Requires Ca&lt;sup&gt;2+&lt;/sup&gt;-Dependent Metalloproteinase Activity

Pittman, Randall N.; Williams, Alison G.

doi:10.1159/000111884

Cited by 62 publications

(32 citation statements)

References 34 publications

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“…It has been shown that neurite extension on 3D gels depends upon the gel concentration and resultant mechanical stiffness (Balgude et al, 2001;O'Connor et al, 2001;Willits and Skornia, 2004), the presence of ECM molecules , and Ca 21 -dependent metalloproteinase from the growth cones (Pittman and Williams, 1989). Li and Folch (2005) showed that preferential growth of the axon tips is for a straight path, but also for a poly-D-lysine substrate over one with Matrigel.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Axonal Growth into Collagen Nerve Guides Containing VEGF‐Transfected Stem Cells in Matrigel

Kempton

Gonzalez

Leven

et al. 2008

The Anatomical Record

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The early events associated with axonal growth into 10-mm nerve gaps were studied histologically in the rat sciatic nerve model to determine if the outgrowth of blood vessels, Schwann cells, and axons could be enhanced. In the first two experimental groups, collagen nerve guides were filled with either saline or Matrigel. Marrow-derived mesenchymal stem cells (MSCs) were added to Matrigel in two other groups, one of which contained cells transfected with VEGF (MSC/VEGF). After 21 days, the injury site was exposed, fixed, sectioned, and volume fractions of the conduit contents were determined by point counting. The bioresorbable collagen conduits appropriately guided the axons and vessels in a longitudinal direction. The volume fraction of axons was significantly greater in the group with saline when compared with all three groups with Matrigel. This measure had a significant positive correlation with actual counts of myelinated axons. The blood vessel volume fraction in the Matrigel group decreased compared with the saline group, but was restored in the MSC/VEGF group. All Matrigel groups had comparable cellularity and showed a distribution of residual Matrigel in acellular zones. The saline group, by contrast, sustained a network of delicate fibroblastic processes that compartmentalized the nerve and its natural matrix as it became infiltrated by axons as minifascicles. In conclusion, the reduction of axonal outgrowth in the Matrigel groups, when compared with the saline group, suggests that Matrigel may impede the early regenerative process even when enriched by the addition of MSCs or VEGF-transfected cells.

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Section: Discussionmentioning

confidence: 99%

Assessment of Axonal Growth into Collagen Nerve Guides Containing VEGF‐Transfected Stem Cells in Matrigel

Kempton

Gonzalez

Leven

et al. 2008

The Anatomical Record

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“…Neuronal proteases have been reported to be localized to distal processes and neurite growth cones (7,41,42), and protease inhibitors have been shown to inhibit neurite outgrowth in three-dimensional matrices (43,44). The pattern of Ann-II expression within the developing nervous system (24) displays striking spatial and temporal similarities with that of t-PA expression (6).…”

Section: Discussionmentioning

confidence: 99%

“…Most MMPs are secreted as proenzymes and are activated in a stepwise manner under certain pathological and physiological conditions requiring matrix remodeling (50). In cultured rat sympathetic neurons, a metalloproteinase released from the neurite growth cone was essential for neurite penetration into a three-dimensional collagen matrix (41). NGF-treated embryonic chick DRG cultures also expressed a metalloproteinase whose activity enhanced neurite penetration within a reconstituted matrix (44).…”

Section: Discussionmentioning

confidence: 99%

Neuritogenesis and the Nerve Growth Factor-induced Differentiation of PC-12 Cells Requires Annexin II-mediated Plasmin Generation

Jacovina¹,

Zhong

Khazanova

et al. 2001

Journal of Biological Chemistry

108

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One of the key morphological changes associated with the nerve growth factor (NGF)-induced differentiation of rat adrenal pheochromocytoma (PC-12) cells is the growth of axon-like processes called neurites. A growing body of evidence suggests that this process may be dependent upon plasmin, a serine protease generated from plasminogen (Plg) by either urokinase Plg activator (u-PA) or tissue Plg activator (t-PA). Prior work in our laboratory has identified annexin II (Ann-II) as a coreceptor for Plg and t-PA that promotes and localizes plasmin generation near the cell surface. In the present study, we report a 3-9-fold increase in Ann-II protein and message levels in NGF-treated PC-12 cells. Message stability and nuclear run-on assays suggest that this induction occurs at the level of gene transcription. Neurite outgrowth assays on and within a three-dimensional matrix demonstrate the inhibition of NGF-induced PC-12 cell differentiation by polyclonal and monoclonal antibodies directed against Ann-II as well as by the overexpression of antisense Ann-II mRNA. Neuritogenesis is also impaired by ␣ 2 -plasmin inhibitor, antibodies directed against t-PA and u-PA, and ⑀-aminocaproic acid, a lysine analog that inhibits Plg activation and the binding of Plg to Ann-II. Plasmin generation assays reveal a 2-fold increase in plasmin production on NGF-treated PC-12 cells, which can be blocked by a polyclonal antibody directed against the tail region of Ann-II. From these data, we conclude that Ann-II is transcriptionally up-regulated by NGF and that Ann-II-mediated plasmin generation may play an important role during neurite development in the differentiating PC-12 cell.

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“…For example, plasminogen activators have been shown to be produced and secreted by neurons and glia and to participate in remodeling events that occur during cell migration (Moonen et al, 1982), neurite outgrowth (Monard, 1988;Pittman and Williams, 1989;Sumi et al, 1992;Sappino et al, 1993), and synaptic plasticity (Monard, 1988;Qian et al, 1993;Sappino et al, 1993). MSP Table 1.…”

Section: Region and Cell-specific Expression Of Msp In The Cnsmentioning

confidence: 99%

“…The activity of serine proteases and their inhibitors has been established to play important roles in the nervous system, including the regulation of neuronal migration during development (Moonen et al, 1982;Seeds et al, 1990), neurite outgrowth (Monard, 1988), synaptic plasticity (Liu et al, 1994a,b), and neuronal degeneration and death (Houenou et al, 1995;Tsirka et al, 1995Tsirka et al, , 1997. These actions may be mediated by the proteolytic cleavage of zymogen precursors and propeptides, the activation of specific cell surface receptors, and /or by the degradation of extracellular matrix proteins (Monard, 1988;Pittman and Williams, 1989;McGuire and Seeds, 1990).…”

mentioning

confidence: 99%

Nervous System-Specific Expression of a Novel Serine Protease: Regulation in the Adult Rat Spinal Cord by Excitotoxic Injury

1997

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A full-length cDNA clone of a previously unidentified serine protease, myelencephalon-specific protease (MSP), has been isolated by using a PCR cloning strategy and has been shown to be expressed in a nervous system and spinal cord-specific pattern. Sequence analysis demonstrated that MSP is most similar in sequence to neuropsin, trypsin, and tissue kallikrein and is predicted to have trypsin-like substrate specificity. MSP mRNA was found to be ϳ10-fold greater in the CNS of the rat and human, as compared with most peripheral tissues, and within the CNS was found to be highest by a factor of four in the medulla oblongata and spinal cord. Levels of mRNA encoding tissue plasminogen activator (tPA) also were elevated in the spinal cord but were more widespread in peripheral tissues as compared with MSP.In the adult rat lumbosacral spinal cord, in situ localization of MSP mRNA demonstrated 2-fold higher levels in the white, as compared with the gray, matter. MSP mRNA expression was shown to increase 3-fold in the white matter and 1.5-fold in the gray laminae at 72 hr after intraperitoneal injection of the AMPA/ kainate glutamate receptor-specific agonist, kainic acid (KA). MSP mRNA remained elevated in the ventral gray matter, including expression associated with the motor neurons of lamina IX, at 7 d after the initial excitotoxic insult. Together, these observations indicate that MSP is in a position to play a fundamental role in normal homeostasis and in the response of the spinal cord to injury.

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Neurite Penetration into Collagen Gels Requires Ca<sup>2+</sup>-Dependent Metalloproteinase Activity

Cited by 62 publications

References 34 publications

Assessment of Axonal Growth into Collagen Nerve Guides Containing VEGF‐Transfected Stem Cells in Matrigel

Assessment of Axonal Growth into Collagen Nerve Guides Containing VEGF‐Transfected Stem Cells in Matrigel

Neuritogenesis and the Nerve Growth Factor-induced Differentiation of PC-12 Cells Requires Annexin II-mediated Plasmin Generation

Nervous System-Specific Expression of a Novel Serine Protease: Regulation in the Adult Rat Spinal Cord by Excitotoxic Injury

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