Role of the prostaglandin E2/E-prostanoid 2 receptor signalling pathway in TGFβ-induced mice mesangial cell damage

Area of Science:

• Nephrology
• Molecular Biology
• Cell Biology

Background:

• Glomerular mesangial cells (MCs) are crucial in kidney function.
• Transforming growth factor-β1 (TGFβ1) induces MC damage, but mechanisms are unclear.
• Prostaglandin E2 receptor EP2's role in this process is unknown.

Purpose of the Study:

• To investigate the EP2 signaling pathway's role in TGFβ1-induced MCs proliferation, extracellular matrix (ECM) accumulation, and prostaglandin E2 synthase (PGES) expression.
• To elucidate the molecular mechanisms underlying EP2's protective effects against TGFβ1-induced MC damage.

Main Methods:

• Primary mouse MCs were cultured and treated with TGFβ1.
• EP2 deficiency was induced using EP2-siRNA (small interfering RNA).
• EP2 overexpression was achieved using Adenovirus-mediated gene transfer.
• Key proteins and gene expressions (FN, Col I, COX2, mPGES-1, CTGF, CyclinD1, p38MAPK, ERK1/2, CREB1) were analyzed.

Main Results:

• TGFβ1 increased MCs proliferation but decreased cAMP and prostaglandin E2 (PGE2) production.
• EP2 deficiency exacerbated TGFβ1-induced expression of fibronectin (FN), collagen type I (Col I), COX2, mPGES-1, CTGF, and CyclinD1.
• Silencing EP2 enhanced TGFβ1-induced phosphorylation of p38MAPK, ERK1/2, and CREB1.
• EP2 overexpression reversed these effects.

Conclusions:

• EP2 activation, via cAMP production and PGE2 stimulation, inhibits TGFβ1-induced MC damage.
• EP2 signaling blocks p38MAPK, ERK1/2, and CREB1 phosphorylation, thereby preventing MC injury.
• Targeting EP2 receptors may offer a therapeutic strategy against TGFβ1-mediated kidney damage.