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Studies on the Effects of Phosphodiesterase 4 Inhibition on Diabetic Nephropathy Using Model Mice

大川原, 賦 筑波大学 DOI:10.15068/0002008132

2023.09.04

概要

Diabetic nephropathy (DN) is a major microvascular complication in patients with diabetes
mellitus, which leads to chronic kidney diseases and end-stage renal failure worldwide [1].
Renin-angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors
and angiotensin II receptor blockers (ARBs), are widely used to treat patients with DN.
However, these agents cannot completely prevent the progression of kidney disease, and disease
conditions will therefore eventually progress to end-stage kidney disease in many patients [10].
Thus, there is still a high unmet medical need for new treatment options for this disease
condition. Since DN is associated with hyperglycemia, insulin resistance, chronic inflammation,
and fibrosis, new drugs that can suppress these pathological insults could be a new treatment
option. Phosphodiesterase (PDE) 4 is an enzyme class that selectively hydrolyzes cAMP, a
secondary messenger for intracellular signaling, and activates various cellular events via the
protein kinase A and exchange protein directly activated by cAMP (Epac) pathways, including
anti-inflammatory and anti-fibrotic effects [25, 26]. Sisson et al. showed that the PDE4
inhibitor, compound A, reduced lung fibrosis following targeted type II alveolar epithelial cell
injury [27]. ...

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