Abstract: FR-PO959
Hematopoietic Cell Kinase (HCK) Is a Key Regulator of Macrophage Function in Kidney Fibrosis
Session Information
- CKD: Pathobiology - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Wei, Chengguo, Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States
- Chen, Man, Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States
- Zhang, Weijia, Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States
- Lee, Kyung, Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States
- He, John Cijiang, Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States
Background
Our previous study identified HCK as a regulator of renal fibrosis. We recently find HCK could regulate autophagy in macrophages. Here we tested HCK's role in macrophage function in the context of renal fibrosis.
Methods
Bone marrow-derived macrophage (BMDM) and RAW264.7 macrophage in vitro and UUO in vivo for global, macrophage HCK-KO and WT mice were used to determine the effects of HCK on macrophage autophagy and activation.
Results
Single cell sequencing data confirmed that HCK is mainly expressed in macrophages (Fig. 1A). IP/MS identified HCK interacts with autophagy proteins ATG2A and CBL(data not shown) and confirmed by IP/WB (Fig. 1B) in macrophage cell line RAW264.7. KO of HCK increased autophagy activity as increased LC3II/LC3I ratio and decreased P62 in BMDM (Fig. 1C). We also found KO of HCK decreased macrophage M1 polarization and increased M2 polarization in BMDM by qPCR, WB(Fig. 1D, 1E), and flow cytometry (Fig. 1F). In the UUO model, we found that global and macrophage-specific HCK-KO mice had significantly attenuated tubulointerstitial fibrosis with decreased mRNA profibrotic markers (Fig. 2C) and Masson’s trichrome staining (Fig. 2D, 2E).
Conclusion
HCK promotes kidney fibrosis by suppressing macrophage autophagy and inducing macrophage polarization.