Sugioka Koji, Nishida Teruo, Murakami Junko, Itahashi Motoki, Yunoki Mai, Kusaka Shunji
Department of Ophthalmology, Kindai University Nara Hospital, Ikoma, Japan.
Department of Ophthalmology, Kindai University Faculty of Medicine, Osakasayama, Japan.
Am J Physiol Cell Physiol. 2024 May 1;326(5):C1482-C1493. doi: 10.1152/ajpcell.00084.2024. Epub 2024 Mar 25.
Corneal fibroblasts maintain homeostasis of the corneal stroma by mediating the synthesis and degradation of extracellular collagen, and these actions are promoted by transforming growth factor-β (TGF-β) and interleukin-1β (IL-1β), respectively. The cornea is densely innervated with sensory nerve fibers that are not only responsible for sensation but also required for physiological processes such as tear secretion and wound healing. Loss or dysfunction of corneal nerves thus impairs corneal epithelial wound healing and can lead to neurotrophic keratopathy. The sensory neurotransmitter substance P (SP) promotes corneal epithelial wound healing by enhancing the stimulatory effects of growth factors and fibronectin. We have now investigated the role of SP in collagen metabolism mediated by human corneal fibroblasts in culture. Although SP alone had no effect on collagen synthesis or degradation by these cells, it promoted the stimulatory effect of TGF-β on collagen type I synthesis without affecting that of IL-1β on the expression of matrix metalloproteinase-1. This effect of SP on TGF-β-induced collagen synthesis was accompanied by activation of p38 mitogen-activated protein kinase (MAPK) signaling and was attenuated by pharmacological inhibition of p38 or of the neurokinin-1 receptor. Our results thus implicate SP as a modulator of TGF-β-induced collagen type I synthesis by human corneal fibroblasts, and they suggest that loss of this function may contribute to the development of neurotrophic keratopathy. This study investigates the role of substance P (SP) in collagen metabolism mediated by human corneal fibroblasts in culture. We found that, although SP alone had no effect on collagen synthesis or degradation by corneal fibroblasts, it promoted the stimulatory effect of transforming growth factor-β on collagen type I synthesis without affecting that of interleukin-1β on the expression of matrix metalloproteinase-1.
角膜成纤维细胞通过介导细胞外胶原蛋白的合成和降解来维持角膜基质的稳态，而这些作用分别由转化生长因子-β（TGF-β）和白细胞介素-1β（IL-1β）促进。角膜密布着感觉神经纤维，这些神经纤维不仅负责感觉，而且对于诸如泪液分泌和伤口愈合等生理过程也是必需的。因此，角膜神经的丧失或功能障碍会损害角膜上皮伤口愈合，并可能导致神经营养性角膜病变。感觉神经递质P物质（SP）通过增强生长因子和纤连蛋白的刺激作用来促进角膜上皮伤口愈合。我们现在研究了SP在培养的人角膜成纤维细胞介导的胶原代谢中的作用。尽管单独的SP对这些细胞的胶原蛋白合成或降解没有影响，但它促进了TGF-β对I型胶原蛋白合成的刺激作用，而不影响IL-1β对基质金属蛋白酶-1表达的作用。SP对TGF-β诱导的胶原蛋白合成的这种作用伴随着p38丝裂原活化蛋白激酶（MAPK）信号通路的激活，并被p38或神经激肽-1受体的药理学抑制所减弱。因此，我们的结果表明SP是人角膜成纤维细胞TGF-β诱导的I型胶原蛋白合成的调节剂，并且表明这种功能的丧失可能导致神经营养性角膜病变的发展。本研究调查了P物质（SP）在培养的人角膜成纤维细胞介导的胶原代谢中的作用。我们发现，尽管单独的SP对角膜成纤维细胞的胶原蛋白合成或降解没有影响，但它促进了转化生长因子-β对I型胶原蛋白合成的刺激作用，而不影响白细胞介素-1β对基质金属蛋白酶-1表达的作用。
