The role of TCPTP on leptin effects on astrocyte morphology

Mol Cell Endocrinol. 2019 Feb 15:482:62-69. doi: 10.1016/j.mce.2018.12.010. Epub 2018 Dec 17.

Abstract

Leptin and LPS has been implicated in the development of hypothalamic astrogliosis in rodents. Astrocytes, which are interconnected by gap junction proteins, have emerged as important players in the control of energy homeostasis exerted by the hypothalamus. To investigate the hypothesis of action of T-cell protein tyrosine phosphatase (TCPTP) on the astrocyte morphology, astrocytes from the hypothalamus of one-day-old rats were stimulated with leptin and LPS (used as a positive control). Leptin and LPS induced a marked increase in astrocyte size, an increase in Ptpn2 (TCPTP gene) and gap junction alpha-1 protein, - Gja1 (connexin 43 - CX43 gene) mRNA expression and a decrease in gap junction protein, alpha 6 - Gja6 (CX30 gene) mRNA expression. Remarkably, these effects on astrocytes morphology and connexins were prevented by Ptpn2 siRNA. Astrocytes are known to produce cytokines; here we show that TCPTP acts as an important regulator of the cytokines and it possesses a reciprocal interplay with protein tyrosine phosphatase 1B (PTP1B). Our findings demonstrate that leptin and LPS alter astrocyte morphology by increasing TCPTP, which in turn modulates connexin 30 (CX30) and connexin 43 (CX43) expression. TCPTP and PTP1B seem to act in the regulation of cytokine production in astrocytes.

Keywords: CX30; CX43; Glia; Hypothalamus; Leptin; TCPTP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Astrocytes / cytology*
  • Astrocytes / drug effects
  • Cells, Cultured
  • Connexin 30 / genetics
  • Connexin 43
  • Cytokines / metabolism
  • Hypothalamus / cytology*
  • Hypothalamus / drug effects
  • Leptin / adverse effects*
  • Lipopolysaccharides / adverse effects*
  • Organ Size / drug effects
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 / genetics*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 / metabolism
  • Rats
  • Rats, Wistar
  • Up-Regulation

Substances

  • Connexin 30
  • Connexin 43
  • Cytokines
  • Gja1 protein, rat
  • Gjb6 protein, rat
  • Leptin
  • Lipopolysaccharides
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2
  • Ptpn1 protein, rat
  • Ptpn2 protein, rat