The Role of M2 Macrophages in the Progression of Chronic Kidney Disease following Acute Kidney Injury.

Abstract

INTRODUCTION:

Acute kidney injury (AKI) is a major risk factor in the development of chronic kidney disease (CKD). However, the mechanisms linking AKI to CKD remain unclear. We examined the alteration of macrophage phenotypes during an extended recovery period following ischemia/reperfusion injury (IRI) and determine their roles in the development of fibrosis.

METHODS:

The left renal pedicle of mice was clamped for 40 min. To deplete monocyte/macrophage, liposome clodronate was injected or CD11b-DTR and CD11c-DTR transgenic mice were used.

RESULTS:

Throughout the phase of IRI recovery, M2-phenotype macrophages made up the predominant macrophage subset. On day 28, renal fibrosis was clearly shown with increased type IV collagen and TGF-β. The depletion of macrophages induced by the liposome clodronate injection improved renal fibrosis with a reduction of kidney IL-6, type IV collagen, and TGF-β levels. Additionally, the adoptive transfer of the M2c macrophages partially reversed the beneficial effect of macrophage depletion, whereas the adoptive transfer of the M1 macrophages did not. M2 macrophages isolated from the kidneys during the recovery phase expressed 2.5 fold higher levels of TGF-β than the M1 macrophages. The injection of the diphtheria toxin into CD11b or CD11c-DTR transgenic mice resulted in lesser depletion or no change in M2 macrophages and had little impact on renal fibrosis.

CONCLUSION:

Although M2 macrophages are known to be indispensible for short-term recovery, they are thought to be main culprit in the development of renal fibrosis following IRI.

• Authors: Myung-Gyu Kim, Sun Chul Kim, Yoon Sook Ko, Hee Young Lee, Sang-Kyung Jo, Wonyong Cho
• Journal: PloS one (PLoS One) Vol. 10 Issue 12 Pg. e0143961 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26630505 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Acute Kidney Injury (pathology)
• Animals
• Disease Progression
• Kidney Failure, Chronic (pathology)
• Macrophages (pathology)
• Male
• Mice
• Mice, Inbred C57BL