Oncostatin M Improves Cutaneous Wound Re-Epithelialization and Is Deficient under Diabetic Conditions.
Oncostatin M Improves Cutaneous Wound Re-Epithelialization and Is Deficient under Diabetic Conditions.
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DOI：
10.1016/j.jid.2021.04.039
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Roy S
中科院分区：
文献类型：
--
作者：
Das A;Madeshiya AK;Biswas N;Ghosh N;Gorain M;Rawat A;Mahajan SP;Khanna S;Sen CK;Roy S
以过度角化非迁移性伤口上皮为特征的再上皮化受损是糖尿病伤口不愈合的标志。在慢性伤口中，伤口巨噬细胞大量释放抑癌素M （OSM）是明显的。OSM是一种有效的角质形成细胞激活剂。这项工作旨在了解负责伤口再上皮化的信号转导途径，这是伤口愈合的主要机制。重组小鼠OSM每日局部治疗C57bl/6小鼠全层切除创面，通过促进角化细胞增殖和迁移，改善创面再上皮化，加速创面愈合。OSM激活了JAK-STAT通路，表现为STAT3磷酸化。这种信号转导在人角质形成细胞中诱导了TP63，它是角质形成细胞功能的主要调节因子。TP63升高诱导整合素- 1，一种已知的角质形成细胞迁移的效应因子。与非糖尿病创面相比，糖尿病创面中OSM含量更高。然而，在糖尿病伤口中，OSM活性受到糖基化的损害。氨基胍，一种去糖基化剂，挽救了糖基化OSM引起的受损角质细胞迁移。最后，局部应用重组OSM可改善db/db小鼠的角质细胞迁移并加速伤口愈合。这项工作认识到，尽管OSM在伤口部位丰富，但OSM会因糖化而失活，外源性OSM的局部递送可能会加速糖尿病伤口愈合。
Impaired re-epithelialization characterized by hyperkeratotic non-migratory wound epithelium is a hallmark of non-healing diabetic wounds. In chronic wounds, copious release of oncostatin M (OSM) from wound macrophages is evident. OSM is a potent keratinocyte activator. This work sought to understand the signal transduction pathway responsible for wound-re-epithelialization, the primary mechanism underlying wound closure. Daily topical treatment of full-thickness excisional wounds of C57bl/6 mice with recombinant murine OSM improved wound re-epithelialization and accelerated wound closure by bolstering keratinocyte proliferation and migration. OSM activated the JAK-STAT pathway as manifested by STAT3 phosphorylation. Such signal transduction in the human keratinocyte induced TP63, the master regulator of keratinocyte function. Elevated TP63 induced integrin beta 1, a known effector of keratinocyte migration. In diabetic wounds, OSM was more abundant compared to the level in non-diabetic wounds. However, in diabetic wounds OSM activity was compromised by glycation. Aminoguanidine, a deglycation agent, rescued compromised keratinocyte migration caused by glycated OSM. Finally, topical application of recombinant OSM improved keratinocyte migration and accelerated wound closure in db/db mice. This work recognizes that despite its abundance at the wound-site, OSM is inactivated by glycation and topical delivery of exogenous OSM is likely to be productive in accelerating diabetic wound closure.
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影响因子：
4.6
作者：
Das A;Datta S;Roche E;Chaffee S;Jose E;Shi L;Grover K;Khanna S;Sen CK;Roy S
通讯作者：
Roy S
影响因子：
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作者：
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通讯作者：
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DOI：
10.4049/jimmunol.1502270
发表时间：
2016-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Das A;Ghatak S;Sinha M;Chaffee S;Ahmed NS;Parinandi NL;Wohleb ES;Sheridan JF;Sen CK;Roy S
通讯作者：
Roy S
DOI：
10.1073/pnas.1001653107
发表时间：
2010-04-13
影响因子：
11.1
作者：
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通讯作者：
Sen, Chandan K.
影响因子：
8.2
作者：
Kuzuya, M;Satake, S;Iguchi, A
通讯作者：
Iguchi, A