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PPARγ and TGFβ-Major Regulators of Metabolism, Inflammation, and Fibrosis in the Lungs and Kidneys

Journal

Publisher

MDPI
DOI: 10.3390/ijms221910431

Keywords

PPAR gamma; pulmonary arterial hypertension; TGF beta; vascular injury; inflammation; proliferation; kidney fibrosis

Funding

  1. German Research Foundation [DFG HA4348/6-2 KFO311, HA4348/2-2]
  2. European Pediatric Pulmonary Vascular Disease Network
  3. Federal Ministry of Education and Research [03VP08053, BMBF01KC2001B]
  4. Hungarian Society for Hypertension Scientific Grant
  5. Semmelweis University Innovation Center [STIA-OTKA 137266/TMI/2020]
  6. Bolyai Scholarship of the Hungarian Academy of Sciences
  7. UNKP Bolyai+ Scholarship [UNKP-20-5-SE-3]

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PPAR gamma, initially recognized in adipose tissue for its role in fatty acid storage and glucose metabolism, is also implicated in cardiac development, PAH, and kidney failure. Recent studies have linked PPAR gamma signaling with the TGF beta superfamily, highlighting the complex crosstalk between these pathways in PAH and kidney failure. The therapeutic potential of PPAR gamma agonist pioglitazone is also discussed in the context of these connections.
Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a type II nuclear receptor, initially recognized in adipose tissue for its role in fatty acid storage and glucose metabolism. It promotes lipid uptake and adipogenesis by increasing insulin sensitivity and adiponectin release. Later, PPAR gamma was implicated in cardiac development and in critical conditions such as pulmonary arterial hypertension (PAH) and kidney failure. Recently, a cluster of different papers linked PPAR gamma signaling with another superfamily, the transforming growth factor beta (TGF beta), and its receptors, all of which play a major role in PAH and kidney failure. TGF beta is a multifunctional cytokine that drives inflammation, fibrosis, and cell differentiation while PPAR gamma activation reverses these adverse events in many models. Such opposite biological effects emphasize the delicate balance and complex crosstalk between PPAR gamma and TGF beta. Based on solid experimental and clinical evidence, the present review summarizes connections and their implications for PAH and kidney failure, highlighting the similarities and differences between lung and kidney mechanisms as well as discussing the therapeutic potential of PPAR gamma agonist pioglitazone.

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