{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:44:00Z","timestamp":1760060640257,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T00:00:00Z","timestamp":1758412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"an interior grant","award":["01-SWKJYCJJ32"],"award-info":[{"award-number":["01-SWKJYCJJ32"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Shiga toxins (Stx), produced by Shiga toxin-producing Escherichia coli, preferentially attack renal tissue and frequently induce acute kidney injury (AKI) and renal failure. To prevent irreversible damage, the injured renal tissue, particularly renal tubular epithelium, mounts a remodeling and regeneration response to repair itself. However, how such intrinsic renal repair processes are initiated and coordinated in infected renal tubular regions remains elusive. Herein, we reported that macula densa apparatus, in addition to its conventional role as a salt sensor in nephron, can function as an endogenous sensor for exogenous toxins (e.g., Stx). We demonstrated that macula densa cells orchestrate a rapid repair niche by initiating transcriptional activation of repair and regeneration factors in both Stx-injured murine models and human kidney organoids. Mechanistically, we showed that in response to Stx exposure, macula densa cells release a specific repair factor CCN1, which effectively promotes the regeneration of toxin-injured renal tubular epithelium and facilitates renal tubular repair through integrin-mediated signaling pathways. Moreover, we demonstrated that treatment with recombinant CCN1 can greatly ameliorate the structural damage and significantly restore the proximal tubular reabsorption capacity in Stx-infected kidney organoids. Our finding highlights a novel role of macula densa apparatus in toxin-induced renal injury, and paves a new avenue for treatment of AKI-associated renal diseases.<\/jats:p>","DOI":"10.3390\/toxins17090470","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T11:18:16Z","timestamp":1758539896000},"page":"470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Macula Densa Alleviates Shiga Toxin-Induced Acute Kidney Injury via CCN1-Mediated Renal Tubular Repair"],"prefix":"10.3390","volume":"17","author":[{"given":"Hongzhi","family":"Wan","sequence":"first","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100850, China"},{"name":"Military Medical Sciences Academy, Tianjin 300050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhui","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahui","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical School of Chinese PLA, Beijing 100850, China"},{"name":"Department of Stomatology, The First Medical Center of Chinese PLA General Hospital, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiamei","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Qingdao University, Qingdao 266071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3858-1018","authenticated-orcid":false,"given":"Qisheng","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, First Affiliated Hospital Guangxi Medical University, Nanning 530021, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Peng","sequence":"additional","affiliation":[{"name":"Military Medical Sciences Academy, Tianjin 300050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaotao","family":"Duan","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100850, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13099-024-00641-9","article-title":"Overview of pathogenic Escherichia coli, with a focus on Shiga toxin-producing serotypes, global outbreaks (1982\u20132024) and food safety criteria","volume":"16","author":"Alhadlaq","year":"2024","journal-title":"Gut Pathog."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1016\/S0140-6736(22)01202-8","article-title":"Haemolytic uraemic syndrome","volume":"400","author":"Michael","year":"2022","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"M\u00fchlen, S., and Dersch, P. 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