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. 2019 May 15;9:7414. doi: 10.1038/s41598-019-43576-x

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Proposed schema for the mechanism of renal interstitial fibrosis regulated by ATX-LPA-LPA₁ signaling dependent on interstitial vascular leak. Interstitial vascular leak induced by UUO causes the leakage of ATX into the interstitium. The interstitial ATX then catalyzes the production of LPA which further enhances interstitial vascular leak, thus creating a vicious cycle of LPA-driven renal vascular leak. Additionally, the produced LPA contributes to the accumulation of fibroblasts/myofibroblasts by driving fibroblast migration, proliferation and differentiation dependent on LPA₁. Other pathways would also be involved in LPA production. Besides ATX-LPA₁ signaling, multiple pathways producing LPA could be targets to treat renal interstitial fibrosis.