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The effects of inhibitors of the CCL2\/CCR2 axis, such as anti-CCL2 antibody and CCR2 antagonist, on kidney function in animal models or humans with kidney dysfunction have been demonstrated. The N-terminal glutamine on immature CCL2 is replaced with pyroglutamate (pE) by glutaminyl cyclase (QC) and isoQC. pE-CCL2 is stable and resistant to peptidases. We hypothesized that inhibiting QC\/isoQC activity would lead to the degradation of CCL2, thereby ameliorating CKD and reducing kidney inflammation. To test this hypothesis, we investigated the renoprotective properties of the QC\/isoQC inhibitor PQ529 in anti-glomerular basement membrane (GBM) antibody\u2013induced glomerulonephritis Wistar Kyoto (WKY) rats. Three-week repeated administration of PQ529 (30 and 100\u00a0mg\/kg, twice daily) significantly reduced the serum and urine CCL2 and urinary protein excretion in a dose-dependent manner. Correlations between the urinary protein level and serum or urinary CCL2 levels were confirmed in tested animals. Repeated administration of PQ529 significantly reduced the expression of CD68, a macrophage marker, in the kidney cortex and mononuclear infiltration into the tubulointerstitium. In addition, decreased levels of urinary KIM-1, \u03b22 microglobulin, and clusterin were detected, suggesting the inhibition of inflammation in both the proximal and distal tubules. These results suggest that PQ529 suppresses the progression of inflammation-induced renal dysfunction by inhibiting the CCL2\/CCR2 axis. Inhibition of QC\/isoQC may thus be a viable alternative therapeutic approach for treating glomerulonephritis and CKD patients.<\/jats:p>","DOI":"10.1007\/s00210-020-02013-x","type":"journal-article","created":{"date-parts":[[2020,11,7]],"date-time":"2020-11-07T15:02:44Z","timestamp":1604761364000},"page":"751-761","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Chronic treatment with the (iso-)glutaminyl cyclase inhibitor PQ529 is a novel and effective approach for glomerulonephritis in chronic kidney disease"],"prefix":"10.1007","volume":"394","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7105-8811","authenticated-orcid":false,"given":"Naotoshi","family":"Kanemitsu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiko","family":"Kiyonaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiko","family":"Mizukami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoichi","family":"Maeno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Nishikubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,29]]},"reference":[{"key":"2013_CR1","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1046\/j.1523-1755.2000.00214.x","volume":"58","author":"N Banba","year":"2000","unstructured":"Banba N, Nakamura T, Matsumura M, Kuroda H, Hattori Y, Kasai K (2000) Possible relationship of monocyte chemoattractant protein-1 with diabetic nephropathy. 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