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Endothelin-1 (EDN1) and phospho-Jun-amino-terminal kinase (p-JNK) were up-regulated in Fibro-TSC1\u2212\/\u2212 renal fibroblasts after LPS challenge. Rapamycin, an mTORC1 inhibitor, and bosentan, an EDN1 antagonist, eliminated the difference in renal function between TSC1fl\/fl and Fibro-TSC1\u2212\/\u2212 mice after LPS injection. Rapamycin restored LPS-induced up-regulation of EDN1, endothelin converting enzyme-1 (ECE1), and p-JNK in TSC1-knockdown mouse embryonic fibroblasts (MEFs). SP600125, a Jun-amino-terminal kinase (JNK) inhibitor, attenuated LPS-induced enhancement of EDN1 and ECE1 in TSC1-knockdown MEFs without a change in phospho-S6 ribosomal protein (p-S6) level. The results indicate that mTORC1\u2013JNK-dependent up-regulation of ECE1 elevated EDN1 in TSC1-knockout renal fibroblasts and contributed to improvement of renal function in Fibro-TSC1\u2212\/\u2212 mice with LPS-induced AKI. Renal fibroblast mTORC1 plays an important role in septic AKI.<\/jats:p>","DOI":"10.1042\/cs20180348","type":"journal-article","created":{"date-parts":[[2018,9,5]],"date-time":"2018-09-05T17:06:36Z","timestamp":1536167196000},"page":"2087-2101","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["TSC1 deletion in fibroblasts alleviates lipopolysaccharide-induced acute kidney injury"],"prefix":"10.1042","volume":"132","author":[{"given":"Junhui","family":"Shen","sequence":"first","affiliation":[{"name":"Key Laboratory of Mental Health of the Ministry of Enducation, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China"},{"name":"Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, 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