International journal of colorectal disease · 2011
Chemokine upregulation in response to anal sphincter and pudendal nerve injury: potential signals for stem cell homing.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Salcedo Levilester, Sopko Nikolai, Jiang Hai-Hong, Damaser Margot, Penn Marc, Zutshi Massarat
Аннотация
PURPOSE: Stromal derived factor-1 (SDF-1) and monocyte chemotactic protein-3 (MCP-3) are signals forcing the migration of bone marrow-derived stem cells to ischemic tissue. This study investigates SDF-1 and MCP-3 expression following direct injury to the anal sphincter and pudendal nerve and to determine if these same mechanisms have any role.
METHODS: Chemokine expression was studied after anal sphincter injury in female rats after either a sphincterotomy (n = 15), pudendal nerve crush (PNC; n = 15), sham pudendal nerve crush (n = 15), or acted as unmanipulated controls (n = 5). Analysis was done at 1 h and 10 and 21 days after injury.
RESULTS: After injury, SDF-1 expression increased 40.2 ± 6.42 (P = 0.01) at 1 h and 28.2 ± 2.37 (P = 0.01) at 10 days, respectively, compared to controls. Likewise, MCP-3 expression increased 40.8 ± 8.17 (P = 0.02) at the same intervals compared to controls. After PNC, SDF-1 expression increased 46.4 ± 6.01 (P = 0.02) and 50.6 ± 10.11 (P = 0.01), and MCP-3 expression increased 46.3 ± 7.76 (P = 0.03) and 190.8 ± 22.15 (P = 0.01), respectively, at the same time intervals compared to controls. However, when PNC was compared to sham injured, a significant increase was seen in SDF-1 and MCP-3 at 10 days. At 21 days, PNC compared to sham injured was significantly low in expression for both SDF-1 and MCP-3 (P < 0.05).
CONCLUSIONS: Direct anal sphincter injury results in higher levels of SDF-1 and MCP-3 expression soon after injury, whereas denervation via pudendal nerve crush results in greater SDF-1 and MCP-3 expression 10 days after injury. Chemokine overexpression suggests the potential for cell-based therapeutic strategies.
METHODS: Chemokine expression was studied after anal sphincter injury in female rats after either a sphincterotomy (n = 15), pudendal nerve crush (PNC; n = 15), sham pudendal nerve crush (n = 15), or acted as unmanipulated controls (n = 5). Analysis was done at 1 h and 10 and 21 days after injury.
RESULTS: After injury, SDF-1 expression increased 40.2 ± 6.42 (P = 0.01) at 1 h and 28.2 ± 2.37 (P = 0.01) at 10 days, respectively, compared to controls. Likewise, MCP-3 expression increased 40.8 ± 8.17 (P = 0.02) at the same intervals compared to controls. After PNC, SDF-1 expression increased 46.4 ± 6.01 (P = 0.02) and 50.6 ± 10.11 (P = 0.01), and MCP-3 expression increased 46.3 ± 7.76 (P = 0.03) and 190.8 ± 22.15 (P = 0.01), respectively, at the same time intervals compared to controls. However, when PNC was compared to sham injured, a significant increase was seen in SDF-1 and MCP-3 at 10 days. At 21 days, PNC compared to sham injured was significantly low in expression for both SDF-1 and MCP-3 (P < 0.05).
CONCLUSIONS: Direct anal sphincter injury results in higher levels of SDF-1 and MCP-3 expression soon after injury, whereas denervation via pudendal nerve crush results in greater SDF-1 and MCP-3 expression 10 days after injury. Chemokine overexpression suggests the potential for cell-based therapeutic strategies.