Abstract: FR-PO0224
Involvement of α-Tubulin Detyrosination on Microtubules in the Pathogenesis of Renal Fibrosis
Session Information
- CKD: Mechanisms of Injury and Fibrosis - 2
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Aoki, Ryoya, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
- Tanabe, Katsuyuki, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
- Nakadoi, Takato, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
- Wada, Jun, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
Background
Microtubules have pivotal roles for cellular structure and functions. Detyrosination, a post-translational modification at the C-terminus of α-tubulin, is known to affect several functions of microtubules including intracellular transport and cell differentiation, and is catalyzed by Vasohibins (VASHs) and MATCAP1. In our previous study, detyrosinated α-tubulin (deY-tub) was predominantly expressed in podocytes, whereas tyrosinated α-tubulin expression was extensively observed in tubular cells in the kidney. Increased expression of deY-tub has been reported in heart failure cardiomyocytes and high-grade breast cancer cells. However, whether abnormal expression of deY-tub is involved in kidney diseases remains unclear. In the present study, we examined the expression of deY-tub and potential roles of detyrosinating enzymes in renal fibrosis model.
Methods
In vivo experiments, 8-week-old male C57BL/6J wild-type and Vash2-/- mice were subjected to unilateral ureteral obstruction (UUO) to induce renal fibrosis or sham surgery as controls (n=6 in each group). Nephrectomy was performed at Day 7. In vitro experiments, HK-2 cells cultured in keratinocyte serum-free medium were treated with 10 ng/mL of TGF-β1 for forty-eight hours.
Results
Renal deY-tub expression relative to α-tubulin was markedly increased in UUO compared to control group, and immunoreactivity for deY-tub in the UUO kidney was mainly detected on injured tubules. Consistent with in vivo results, deY-tub expression was significantly increased by TGF-β1 treatment in HK-2 cells. In UUO kidney, mRNA levels of detyrosinating enzyme VASH2 were markedly upregulated. However, interstitial fibrosis was not significantly improved and increased deY-tub expression on renal tubules remained in Vash2-/- UUO mice compared to controls. Meanwhile, protein and mRNA levels of novel detyrosinating enzyme MATCAP1 were significantly increased in UUO kidney and the localization of MATCAP1 expression was similar to that of deY-tub on renal tubules.
Conclusion
This study revealed that tubulin detyrosination is involved in the pathogenesis of renal fibrosis. This process at least partially depends on TGF-β in renal tubular cells and is mediated by not only VASH2 but also MATCAP1.
Funding
- Government Support – Non-U.S.